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Background Inflammation, an important event of cellular defensive system, can be triggered by a variety of factors such as pathogens, allergens, damaged cells and toxic compounds. Inflammation indicates tissue remodeling and repair, and is characterized by redness, heat, swelling, pain and loss of function. Purpose Conventional treatment approaches for treatment of inflammation/mediated disorders are associated with various side effects. Herbal remedies are comparatively safe with few side effects. Therefore, the current review summarizes different phytoconstituents which have exhibited their anti-inflammatory potential in various preclinical studies. Methods Google, PubMed, Web of Science and Scopus database have been searched for potentially relevant literature on plant based anti-inflammatory agents. Search was performed using different key words such as “inflammation”, “herbal drugs”, “anti-inflammatory drugs”, “phytomedicine for inflammation” and “plant derived drugs for inflammation”. Further studies were screened through assessment of abstracts and previously published review articles. Results A number of natural products are reported to exhibit anti-inflammatory property in various preclinical and clinical studies and some of them are currently available as herbal formulations. Prominent phytoconstituents exhibiting anti-inflammatory activity include shagoal (Zingiber officinale Roscoe), curcumin (Curcuma longa L.), boswellic acid (Boswellia serrata Roxb.), quercetin (Allium cepa L.), rosmarinic acid (Rosmarinus officinalis L.), berberine (Coptis chinensis Franch) and catechin (Camellia sinensis (L.) Kuntze). Conclusion Phytoconstituents have been reported to exhibit anti-inflammatory property by targeting enzymes and modulating inflammatory mediators and/or by other pathways. Although various preclinical studies have demonstrated promising results against inflammation, however, further research is required to ensure their safety and efficacy in human beings.

The immune system is one of the main defence mechanisms of the human body. Inadequacy of this system or immunodeficiency results in increased risk of infections and tumours, whereas over-activation of the immune system causes allergic or autoimmune disorders. A well-balanced immune system is important for protection and for alleviation of these diseases. There is a growing interest to maintain a well-balanced immune system, especially after the Covid-19 pandemic. Many biological extracts, as well as natural products, have become popular due to their wide array of immunomodulatory effects and influence on the immune system. Triterpenes, one of the secondary metabolite groups of medicinal plants, exhibit immunomodulatory properties by various mechanisms. Different triterpenes, including components of commonly consumed plants, can promote some protection and alleviation of disease symptoms linked with immune responses and thus enhance overall well-being. This review aims to highlight the efficacy of triterpenes in light of the available literature evidence regarding the immunomodulatory properties of triterpenes. We have reviewed widely investigated immunomodulatory triterpenes; oleanolic acid, glycyrrhizin, glycyrrhetinic acid, pristimerin, ursolic acid, boswellic acid, celastrol, lupeol, betulin, betulinic acid, ganoderic acid, cucumarioside, and astragalosides which have important immunoregulatory properties. In spite of many preclinical and clinical trials were conducted on triterpenes related to their immunoregulatory actions, current studies have several limitations. Therefore, especially more clinical studies with optimal design is essential.

Boswellia serrata is known as Kundur in Unani Medicine and the plant is found in Arabia, South Africa and west Asia. The white to yellow colored aromatic oleo resin gum is obtained from the stem bark of this pant and the main constituents of Boswellia serrata Roxb is Boswellic acid. This article was aimed to investigate and compile the pharmacological profile mentioned in Classical text of Unani medicine with special attention to its ulcer healing action and to scientifically recognize those pharmacological actions through the already published scientific studies. Pharmacological activities of kundur mentioned in Unani medicine are astringent, desiccative to the ulcer, antiseptic, haemostatic, cicatrizant, memory tonic, siccative to the secretion of phlegm, carminative, tissue formation and ulcer healing action. The active constituents of Boswellia serrata had proved effective in many experimental and clinical studies for various disease conditions.

Background and Aim: The literature is scant on the effect of 11-keto-β-boswellic acid (KBA) on the liver of diabetes-induced mice. This study was designed to develop a rapid, sensitive, accurate, and inexpensive detection technique for evaluating the solubility of KBA obtained from the gum resin of Omani frankincense (Boswellia sacra) in the liver of streptozotocin-induced diabetic mice using Fourier transform infrared (FTIR) reflectance spectroscopy coupled with principal components analysis (PCA). It also aimed to investigate the effect of KBA on histological changes in the hepatocytes of diabetic mice. Materials and Methods: Eighteen mice were assigned to the healthy control group, the diabetic control group, or the KBA-treated diabetic group. Liver tissue samples from all groups were scanned using an FTIR reflectance spectrophotometer in reflection mode. FTIR reflectance spectra were collected in the wavenumber range of 400-4000 cm-1 using an attenuated total reflectance apparatus. Results: FTIR reflectance spectra were analyzed using PCA. The PCA score plot, which is an exploratory multivariate data set, revealed complete segregation among the three groups' liver samples based on changes in the variation of wavenumber position in the FTIR reflectance spectra, which indicated a clear effect of KBA solubility on treatments. Histological analysis showed an improvement in the liver tissues, with normal structures of hepatocytes exhibiting mild vacuolation in their cytoplasm. Conclusion: KBA improved the morphology of liver tissues in the diabetic mice and led to complete recovery of the damage observed in the diabetic control group. FTIR reflectance spectroscopy coupled with PCA could be deployed as a rapid, low-cost, and non-destructive detection method for evaluating treatment effects in diseased liver tissue based on the solubility of KBA.

The resin of the tree Boswellia sacra Flueck. (synonym: B. carterii; Burseraceae), also known as "frankincense", is a traditional remedy used for central nervous system disorders in East Africa. Here we report the evaluation of its antiseizure activity in zebrafish and mouse epilepsy models to identify novel antiseizure compounds. The resin was extracted by solvents of increasing polarity. The hexane extract demonstrated the strongest antiseizure activity and was therefore subjected to bioactivity-guided isolation, which leaded to the isolation of eight terpene derivatives. A new prenylbicyclogermacrene derivative (2) was isolated along with seven other compounds (1, 3-8). Among them, the triterpene β-boswellic acid (5) showed the strongest activity and reduced 90% of pentylenetetrazole (PTZ)-induced seizures at 100 μg/mL. In parallel to B. sacra, a commercial extract of Boswellia serrata was also evaluated and showed moderate bioactivity (45% reduction at 30 μg/mL). The extract of B. serrata was subjected to targeted isolation of other boswellic acid derivatives (9-13), which were evaluated for antiseizure activity in comparison with 5. In the whole series, β-boswellic acid (5) was the most active (60% reduction at 200 μM), and its potency was also confirmed with its purchased standard (S5). Pure nanoparticles of S5 and a commercially formulated extract of B. serrata were tested in a PTZ-kindling mouse seizure model. This notably revealed that the S5 administration reduced seizures by 50% in this mouse model, which was consistent with its detection and quantification in plasma and brain samples. This study and the preclinical evaluation performed indicate that β-boswellic acid, common to various species of Boswellia, has some potential as an antiseizure agent.

Background: Purified fractions from a Boswellia serrata Roxb. Ex. Colebr. (Burseraceae) extract (ETOH and DCM) contain biologically active compounds that are well known for having inflammation inhibitory properties. In this work, the purified fractions were tested in-vitro for LTC4, LTA4 and COX-2 activities using ELISA and qPCR was performed to determine gene regulation in human leukemia (HL-60) Cells. Two D-imaging tomography was performed to determine the anti-inflammatory activities of the fractions in BALB/c mouse model of lung inflammation. Objective: To evaluate anti-inflammatory activities of bioactive compounds of Boswellia serrata purified fractions. Methods: In-vitro MTT assay was performed in HL-60 cell lines for measuring the toxicity/ viability of the cells. ELISA tests were performed for evaluating LTA4, LTC4 and COX-2 activities. qPCR was performed to evaluate the expression of mRNA in HL-60 cells. In-vivo experiments were performed in OVA sensitized and challenged BALB/c mice at two doses of Boswellia serrata purified fraction containing 6% Boswellic acid of 50 and 100mg/kg body weight were given orally and the standard drug dexamethasone (DXA, 4 mg/kg body weight) and reduction in lung inflammation was assessed by using an IVIS Xenogen in-vivo fluorescence imaging system. Results: A purified fraction of Boswellia serrata ETOH extracts reduced leukotriene-C4-synthase activity by 52%, leuktotriene-A4-hydrolase activity by 22% and COX-2 activity by 99% with an IC50 of 12.5μg/ml. Intragastric administration of the purified fraction of Boswellia serrata at two doses of 50mg/kg b.w. and 100mg/kg b.w., respectively along with 2-3% HPMC resulted in a ~51% (P value Conclusion: The present study describes that Boswellia serrata ethanolic extracts purified fraction (ETOH-BS) possess significant anti-inflammatory activities in HL-60 and in BALB/c and further supports for its use as Ayurvedic medicines traditionally in the treatment of lung disorders including allergy and asthma.

Omani (Dhofari) frankincense is world famous for its high quality and fragrance. The oleo-gum resin obtained from the tree of Omani species i.e., Boswellia sacra (local name: luban) is widely used by the natives. The aim of the study was to determine the presence of phytochemicals in chloroform and ethanol extracts of B. sacra resin and to evaluate the in vitro cytotoxic, antimicrobial- and antioxidant-activities. The ethanol and chloroform extracts of Hojari luban were obtained in good yield. The extracts were subjected to phytochemical screenings, quantification of total phenolics (TP) and evaluation of in vitro biological activities viz. antioxidant, antibacterial and cytotoxic potential. The bioactivities of four boswellic acids, the major constituents of the oleo-gum resin, were also predicted with the help of PASS and CLC-pred software. Both the extracts showed similar level of TP (14.67 mg/g and 14.79 mg/g in terms of gallic acid equivalent) but polar fraction was noted to be more active against E. coli. A moderate antioxidant activity was shown by the resin extracts however their cytotoxic activity was observed to be quite remarkable at 1000 μg/l which could be attributed to their high boswellic acid content. Results of in silico PASS studies showed boswellic acids to possess an array of useful biological activities including chemopreventive activity. Further, CLC-pred software revealed that only keto boswellic acid is expected to exert antineoplastic activity against pancreatic carcinoma cell lines, however all the four major boswellic acids are likely to be active against non-tumor embryonic lung fibroblast (MRC5). The study confirmed that frankincense is rich in bioactive metabolites which are of significant economic and therapeutic importance. Dhaka Univ. J. Pharm. Sci. 19(2): 105-110, 2020 (December)

The article deals with the results of a study of a plant mixture from an ancient vessel found in the rich burial of the Isakovka I burial ground (the Gorkovsky district of the Omsk region, the right bank of the Irtysh River). According to archaeological material, the estimated date of the complex might be not earlier than the 1st–2nd centuries AD. The analysis of the substance was carried out by gas chromatography with mass spectrometric detection (GC–MS) after acid methanolysis. The mixture contains aliphatic lipids (fatty acids, phytosterol), terpenes (monoterpenes, sesquiterpenes, diterpenes and triterpenes) derived apparently from the large amounts of essential oils and resins of plant origin. The presence of a number of diagnostic compounds in the mixture composition (boswellic acid derivatives, amyrins, lupeol) suggests that frankincense from Boswellia resin is included in the mixture. Since psychotropic substances (cannabinoids and nicotinoids) have not been found, this combination may be characteristic of an aroma mixture or incense based on frankincense from Boswellia.

Inflammation plays a major role in chronic airway diseases like asthma, COPD, and cystic fibrosis. Inflammation plays a crucial role in the worsening of the lung function resulting in worsening symptoms. The inflammatory process is very complexed, therefore the strategies for developing an effective treatment for inflammatory airway diseases would benefit from the use of natural substances. : Parthenolide, apocynin, proanthocyanidins, and boswellic acid present different mechanisms of actions - among others, through NF-κB or NADPH oxidase inhibition, therefore showing a wide range of applications in various inflammatory diseases. Moreover, some of them have also antioxidant properties. : Naturally occurring substances may exert some anti-inflammatory effects by modulating some of the inflammatory pathways. These agents have been used in different cultures for thousands of years and have proven to be relatively safe. : Parthenolide, apocynin, proanthocyanidins, and boswellic acid present different mechanisms of actions - among others, through NF-þB or NADPH oxidase inhibition, therefore showing a wide range of applications in various inflammatory diseases. Moreover, some of them have also antioxidant properties. : This review provides an overview of the anti-inflammatory effects of some of the natural agents and illustrates their great potential as sources of drugs to cover an extensive range of pharmacological effects.

Background: Osteoarthritis (OA) is a joint disease involving articular cartilage degeneration causing patients pain, joint stiffness, physical disability, and significantly reducing their quality o...

The oleo gum resin of Boswellia sacra Fleuck. (Burseraceae) is widely consumed for treatment of several diseases and disorders. To determine the effect of repeated administration of this resin on liver and kidney functions, three different doses of standardized methanolic extract were administered orally to rats for 28 days. Apart from histological studies and determination of biomarkers of hepatotoxicity and nephrotoxicity, other parameters of sub-chronic toxicity such as behavioral change, food consumption and change in body weight were assessed. The extract contained about 36.91% of total boswellic acids; of which 11-keto beta boswellic acid, acetyl-11-keto beta boswellic acid, boswellic acids (α and β) and acetyl boswellic acid (α and β) were found to be 5.81%, 1.91%, 21.92% and 7.27% respectively. Oral administration of the extract for 28 consecutive days did not show any sign of behavioral toxicity and did not affect food consumption or weight gain significantly. Determination of biomarkers of hepatic and nephrotoxicity revealed that extract was safe at the tested doses as it did not produce any significant change in the studied biomarkers except producing a dose dependent increase in serum total protein levels. The histological examination supported biochemical findings. To conclude, methanolic extract of Boswellia sacra doen not produce any significant toxicity to liver and kidney up to doses of 100 mg/kg body weight. The results contradict earlier reports that members of boswellia species produce organ toxicity in rats. Keywords: Frankincense, Boswellic acid, Biomarkers, Sub-chronic toxicity, HPLC

3-Acetyl-11-keto-β-boswellic acid (AKBA), a pentacyclic triterpenic acid present in gum resin of Boswellia serrata, has been found to possess antioxidant and neuroprotective properties. In this study, we aimed to examine protective properties of AKBA against glutamate-induced neuronal injury. To investigate the effects of AKBA (2.5-10 µM) on glutamate injury in neuron-like cells PC12 and N2a, two treatment regimens (incubation for 2 or 0 hours before glutamate exposure) were used. Then, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to determine viability of the cells. Cellular redox status was evaluated using fluorimetry and comet assays. Annexin V/propidium iodide double staining and Western blot analysis of relative apoptotic proteins were conducted. Based on the results, 24 hours incubation with glutamate (8 mM) increased the cell mortality of PC12 and N2a (P < .001). However, AKBA (2.5-10 µM) enhanced the cell viability in both treatment regimens (P < .001). Also co- and pretreatment with AKBA significantly attenuated lipid peroxidation, reactive oxygen species production, and DNA injury (P < .05 and P < .001). AKBA also restored the activity of cellular superoxide dismutase under glutamate toxicity; this effect was seen to be more significant during the pretreatment regimen (P < .001). Moreover, Western blot analysis indicated that AKBA inhibited glutamate-induced programmed cell death through depressing the elevation of the expression ratio of Bax/Bcl-2 and cleaved-caspase-3 proteins, concentration-dependently. Overall, the present findings suggest the neuroprotective activities of AKBA against glutamate-induced cell injury probably by inhibiting oxidative damage and reducing apoptotic cell death.

Boswellia serrata is a widely used herb in Indian systems of medicine and is well known for its potential medicinal properties. A chromatographic method was developed for the analysis and quantification of six boswellic acid marker compounds, i.e., keto boswellic acid (1), 3-O-Acetyl 11-keto β-boswellic acid (2), ɑ-Boswellic acid (3), β-Boswellic acid (4), 3-O-Acetyl-ɑ-boswellic acid (5) and 3-O-Acetyl-β-boswellic acid (6) in commercial herbal products containing B. serrata as an ingredient. Combining UPLC with Q-Tof-MS/MS makes the better identification of secondary metabolites and adulterants in the herbal formulations containing B. serrata in rapid time using fragmentation approach than the traditional approaches. In this study quantification of boswellic acids with UPLC-PDA method was performed as per the pharmacopeia guidelines. Furthermore, minor phytochemical constituents were identified and characterized with the help of LC-Q-Tof-MS/MS fragmentation data and various isoforms of boswellic acids and tirucallic acids in B. serrata oleo-gum-resin extract were identified., Graphical abstract Image 1, Highlights • Development of UPLC-PDA method followed by Tof-MS/MS analysis for secondary metabolites characterization. • Quantification of six boswellic acids in crude extract & commercial herbal products available in the market. • Comprehensive analysis of crude extract using UPLC-Q-Tof-MSe. • Identification 16 secondary metabolites from Tof-MS/MS fragmentation pattern.

Hepatocellular carcinoma (HCC) is a primary malignancy of hepatocyte. Boswellic acids are the effective components of gum resin of Boswellia serrata, which have anti-inflammatory properties. Cisplatin is used as a chemotherapeutic agent for treatment of HCC. The present study aims to evaluate the role of Boswellic acid in HCC treatment and as a chemo-sensitizer for Cisplatin treatment of HCC in rats that is induced by orally administration of Diethyl nitrosamine (DEN). Sixty rats were divided in to sex groups, 10 rats each, group 1: normal control group, group 2: cisplatin (1.5 mg/Kg b.wt), group 3: received the Diethyl nitrosamine (DEN) (20 mg/kg b.wt), group 4: received DEN as in group 3 and then treated with cisplatin, group 5: received DEN as in group 3 and then treated with Boswellic acid (500 mg/kg b.wt) and group 6: received DEN as in group 3 and then treated with cisplatin and Boswellic acid. After 10 weeks animals were sacrificed and liver tissue were removed for Histopathological and tissue parameters examination. A significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, a significant decrease in serum albumin concentration. Also a significant increases in liver transforming growth factor-beta 1 (TGF-b1), B-cell lymphoma 2 (Bcl-2) and nuclear factor kappa β (NF-kβ) concentrations and a significant decrease in Caspase.3 activity were recorded in DEN-treated rats while treatment with Boswellic acid and Cisplatin reduced the severity of HCC and enhanced histopathological findings, these result suggesting the efficacy of Boswellic acid supplementation as an anti-HCC.

The resin/gum of Boswellia species belonging to the family of Burseraceae is a naturally occurring mixture of bioactive compounds, which was traditionally used as a folk medicine to treat conditions like chronic inflammation. Several research studies have also explored its' therapeutic potential against multiple neurodegenerative diseases such as Alzheimer's disease (AD). The main chemical constituents of this gum include boswellic acids (BAs) like 3-O-acetyl-11-keto-β boswellic acid (AKBA) that possess potent anti-inflammatory and neuroprotective properties in AD. It is also involved in inhibiting the acetylcholinesterase (AChE) activity in the cholinergic pathway and improve choline levels as well as its binding with nicotinic receptors to produce anti-inflammatory effects. Multiple shreds of evidence have demonstrated that BAs modulate key molecular targets and signalling pathways like 5-lipoxygenase/cyclooxygenase, Nrf2, NF-kB, cholinergic, amyloid-beta (Aβ), and neurofibrillary tangles formation (NFTs) that are involved in AD progression. The present review focuses on the possible mechanistic therapeutic role of BAs in modulating the 5-LOX/COX pathway in arachidonic acid metabolism, activating Nrf2 through binding of ARE, inhibiting NF-kB and AChE activity. In addition, an inhibition of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) induced neurotoxicity and neuroinflammation in AD by BAs is also discussed in this review. We have also highlighted that BAs possess beneficial effects in AD by targeting multiple molecular pathways and makes it an emerging drug candidate for treating neurodegenerative diseases.

Background: Leprosy (Hansen’s disease) is a neglected tropical disease affecting millions of people globally. The combined formulations of dapsone, rifampicin and clofazimine (multidrug therapy, MDT) is only supportive in the early stage of detection, while “reemergence” is a significant problem. Thus, there is still a need to develop newer antileprosy molecules either of natural or semi-synthetic origin. Objective: The review intends to present the latest developments in the disease prevalence, available therapeutic interventions and the possibility of identifying new molecules from phytoextracts. Methods: Literature on the use of plant extracts and their active components to treat leprosy was searched. Selected phytoconstituents were subjected to molecular docking study on both wild and mutant types of the Mycobacterium leprae. Since the M. leprae dihydropteroate synthase (DHPS) is not available in the protein data bank (PDB), it was modelled by the homology model method and validated with the Ramachandran plot along with other bioinformatics approaches. Two mutations were introduced at codons 53 (Thr to Ile) and 55 (Pro to Leu) for docking against twenty-five selected phytoconstituents reported from eight plants that recorded effective anti-leprosy activity. The chemical structure of phytochemicals and the standard dapsone structure were retrieved from the PubChem database and prepared accordingly for docking study with the virtual-screening platform of PyRx-AutoDock 4.1. Results: Based on the docking score (kcal/mol), most of the phytochemicals exhibited a higher docking score than dapsone. Asiaticoside, an active saponin (-11.3, -11.2 and -11.2 kcal/mol), was proved to be the lead phytochemical against both wild and mutant types DHPS. Some other useful phytoconstituents include echinocystic acid (-9.6, -9.5 and -9.5 kcal/mol), neobavaisoflavone (-9.2, -9.0 and -9.0 kcal/mol), boswellic acid (-8.90, -8.90 and -8.90 kcal/mol), asiatic acid (-8.9, -8.8 and -8.9 kcal/mol), corylifol A (-8.8, 8.0, and -8.0), etc. Overall, the computational predictions support the previously reported active phytoextracts of Centella asiatica (L.) Urban, Albizia amara (Roxb.) Boivin, Boswellia serrata Roxb. and Psoralea corylifolia L. to be effective against leprosy. Conclusion: A very small percentage of well-known plants have been evaluated scientifically for antileprosy activity. Further in vivo experiments are essential to confirm anti-leprosy properties of such useful phytochemicals.

In continuation of our search for leads from medicinal plants against protozoal pathogens, we detected antileishmanial activity in polar fractions of a dichloromethane extract from Boswellia serrata resin. 11-keto-β-boswellic acid (KBA) could be isolated from these fractions and was tested in vitro against Leishmania donovani axenic amastigotes along with five further boswellic acid derivatives. 3-O-acetyl-11-keto-β-boswellic acid (AKBA) showed the strongest activity with an IC50 value of 0.88 µM against axenic amastigotes but was inactive against intracellular amastigotes in murine macrophages

Osteoporosis is a systemic metabolic bone disorder that is caused by an imbalance in the functions of osteoclasts and osteoblasts and is characterized by excessive bone resorption by osteoclasts. Targeting osteoclast differentiation and bone resorption is considered a good fundamental solution for overcoming bone diseases. β-boswellic acid (βBA) is a natural compound found in Boswellia serrata, which is an active ingredient with anti-inflammatory, anti-rheumatic, and anti-cancer effects. Here, we explored the anti-resorptive effect of βBA on osteoclastogenesis. βBA significantly inhibited the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by receptor activator of nuclear factor-B ligand (RANKL) and suppressed bone resorption without any cytotoxicity. Interestingly, βBA significantly inhibited the phosphorylation of IκB, Btk, and PLCγ2 and the degradation of IκB. Additionally, βBA strongly inhibited the mRNA and protein expression of c-Fos and NFATc1 induced by RANKL and subsequently attenuated the expression of osteoclast marker genes, such as OC-STAMP, DC-STAMP, β3-integrin, MMP9, ATP6v0d2, and CtsK. These results suggest that βBA is a potential therapeutic candidate for the treatment of excessive osteoclast-induced bone diseases such as osteoporosis.

Triterpenes (30-carbon isoprene compounds) represent a large and highly diverse class of natural products that play various physiological functions in plants. The triterpene biosynthetic enzymes, particularly those catalyzing the late-stage regio-selective modifications are not well characterized. The bark of select Boswellia trees, e.g., B. serrata exudes specialized oleo-gum resin in response to wounding, which is enriched with boswellic acids (BAs), a unique class of C3α-epimeric pentacyclic triterpenes with medicinal properties. The bark possesses a network of resin secretory structures comprised of vertical and horizontal resin canals, and amount of BAs in bark increases considerably in response to wounding. To investigate BA biosynthetic enzymes, we conducted tissue-specific transcriptome profiling and identified a wound-responsive BAHD acetyltransferase (BsAT1) of B. serrata catalyzing the late-stage C3α-O-acetylation reactions in the BA biosynthetic pathway. BsAT1 catalyzed C3α-O-acetylation of αBA, βBA, and 11-keto-βBA in vitro and in planta assays to produce all the major C3α-O-acetyl-BAs (3-acetyl-αBA, 3-acetyl-βBA, and 3-acetyl-11-keto-βBA) found in B. serrata bark and oleo-gum resin. BsAT1 showed strict specificity for BA scaffold, whereas it did not acetylate the more common C3β-epimeric pentacyclic triterpenes. The analysis of steady-state kinetics using various BAs revealed distinct substrate affinity and catalytic efficiency. BsAT1 transcript expression coincides with increased levels of C3α-O-acetyl-BAs in bark in response to wounding, suggesting a role of BsAT1 in wound-induced biosynthesis of C3α-O-acetyl-BAs. Overall, the results provide new insights into the biosynthesis of principal chemical constituents of Boswellia oleo-gum resin.

The study investigated the ability of boswellic acid (BA) to alleviate the testicular and oxidative injury FPN insecticide intoxication in the male rat model. Rats were randomly assigned to six equivalent groups (six rats each) as the following: control rats orally administered with 2 mL physiological saline/kg of body weight (bwt), boswellic acid (BA1) rats orally administered 250 mg BA/kg bwt, boswellic acid (BA2) rats orally administered 500 mg BA/kg bwt, fipronil (FPN) rats orally administered 20 mg FPN/kg bwt, (FPN + BA1) rats orally administered 20 mg FPN/kg bwt plus 250 mg BA/kg bwt, and (FPN + BA2) rats orally administered 20 mg FPN/kg bwt plus 500 mg BA/kg bwt. After 60 days, semen viability percentage and live spermatozoa percentage were decreased, and a considerably increased abnormality of the sperm cells in FPN-administered rats improved substantially with the co-administration of BA. BA had refinement of the histological architecture of testes and sexual glands. Quantitative analysis recorded a noticeable decline in the nuclear cell-proliferating antigen (PCNA) percentage area. FPN triggered cell damage, which was suggested by elevated malondialdehyde and interleukin 6, tumor necrosis factors alpha, and decreased glutathione level. Proapoptotic factor overexpression is mediated by FPN administration, while it decreased the antiapoptotic protein expression. Similarly, BA has shown significant upregulation in steroidogenic and fertility-related gene expression concerning the FPN group. Pathophysiological damages induced by FPN could be alleviated by BA’s antioxidant ability and antiapoptotic factor alongside the upregulation of steroidogenic and fertility-related genes and regimented the detrimental effects of FPN on antioxidant and pro-inflammatory biomarkers.

This study was designed to develop a rapid, sensitive, accurate, and inexpensive Fourier Transform Infrared Reflectance (FT-IR) Spectroscopy coupled with Principle Component Analysis (PCA) as a detection technique to evaluate the solubility of 11-Keto-β-Boswellic acid (KBA), from the gum resin extracted from the Omani frankincense, (Boswellia sacra) in the liver of STZ induced diabetic mice. This study also investigated the effect of KBA on the histological changes of hepatocytes of diabetic mice. Liver tissue samples from three groups of mice included normal control group, diabetic control group and diabetic group treated IP with KBA were scanned with FT-IR spectrophotometer in the reflection mode. FT-IR Spectra were collected in the wavenumber range from 400 to 4000cm-1 using ATR accessorry. The results of FT-IR Spectra were analyzed by using multivariate method Principle Component Analysis. The PCA score plot is an exploratory multivariate method indicated that there was a complete segregation among the three groups of liver samples based on change in variation of position of wavenumber in FT-IR spectra, which revealed that there is a clear effect of KBA solubility on treatments. The histological features showed an improvement in the liver tissues with normal structures of hepatocytes with exhibiting mild vacuolations in their cytoplasm. In conclusion, reflectance FT-IR spectroscopy coupled with PCA could be deployed as a new detection method for rapid, low cost and non-destructive method for evaluating of treatment effects in diseased liver tissue based on the solubility of KBA. Histological findings demonstrated the protective effective of KBA on improving the morphology of liver tissue in diabetic mice which resulted in complete recovery to the damage observed in diabetic control group.Summary StatementReflectance FT-IR spectroscopy coupled with PCA has been deployed as a new rapid, inexpensive and non-destructive detection method to examine the solubility of 11-keto-β-Boswellic acid (KBA) in streptozotocin (STZ) induced-diabetes mice liver tissue following intraperitoneal treatment. Moreover, microscopic study of liver tissue histopathology revealed that KBA has a protecting effect against STZ damage.

Introduction Osteoarthritis is a progressive degenerative joint disease which is high prevalent in dogs. In the late stage of the disease, it determines chronic neuropathic pain which leads to reduced quality-of-life in affected patients. To date it has not yet been identified a specific treatment, but it has been proved that nutraceutical and dietary supplements may play an important role in controlling inflammation and pain. The aim of this study was to evaluate, by the use of force plate gait analysis, the clinical efficacy of Boswellia and Curcuvet® combined with conventional nutraceutical therapy compared with conventional nutraceutical alone in dogs affected by osteoarthritis. Materials and methods Twenty client-owned dogs, over 12 months old and 20 kg of body-weight, with a confirmed diagnosis of Osteoarthritis, were included in this randomized, double-blinded study. The dogs were randomly divided into two groups: the first group (A) received a conventional nutraceutical (consisted in a preparation of glucosamine, chondroitin sulfate, fish-oil containing 80% of omega 3-fatty acid, vitamin C and E, saccharomyces Cerevisiae) with a combination of acid boswellic and Curcuvet®, while the second group (B) received a conventional nutraceutical. All the enrolled dogs underwent a washout period before starting the treatment with nutraceuticals products which were the only admitted treatment over the study period. A full orthopaedic and neurologic examination, and force plate gait analysis were performed before starting the treatment, at 45, 90, and 60 days post-treatment. Ground reaction forces were recorded and analyzed. Results Twenty dogs were enrolled in the study. In both groups there was an increasing values of ground reaction forces. These results might indicate that both nutraceutical products determined a better condition in terms of pain feeling but that effect is much more visible after 60 days from the end of the administration in treated group. Discussion In conclusion Curcuvet in combination with Boswellic acid could be considered a valid aid in a multimodal treatment for canine osteoarthritis.

Boswellic acids are genus specific to Boswellia; they are the principal biologically active compounds holding exceptionally potent anti-inflammatory activity. A series of new 1H-1,2,3-triazole tethered of 3-O-acetyl-β-boswellic acid (ABA, 1) and 3-O-acetyl-11-keto-β-boswellic acid (AKBA, 2) derivatives (10a-d and 11a-d) were synthesized and their carbonic anhydrase II (CA II) inhibitory activity was evaluated in vitro. All compounds were characterized by 1H NMR, 13C NMR, 2D NMR (HMBC, HSQC, COSY and NOESY) experiments, ESI-MS, and when applicable by 19F NMR spectroscopy (10b, 10c and 11b, 11c). This series has displayed a moderate to strong inhibition against CA II with IC50 values of 13.2–60.1 µM. All the active compounds were reported for the first time for their CA II inhibition potential. Kinetics studies on the most active inhibitors (5 and 10b) were carried out to investigate their mode of inhibition and to determine their inhibition constants Ki. Both compounds (5 and 10b) were found to be non-competitive inhibitors with Ki values of 10.40 ± 0.013 and 14.25 ± 0.017 µM, respectively. Molecular docking studies showed that all compounds were well accommodated in the allosteric site of CA II. The current study has demonstrated the usefulness of incorporating a 1H-1,2,3-triazole moiety into the boswellic acids skeleton.

Boswellia serrata is thought of as an Ayurvedic medication and intimate Burseraceae class. The plant is cosmopolitan in India and grows in the dry steep forests of provinces such as Rajasthan, Madhya Pradesh, Gujarat, Bihar, Assam, Orissa, etc. Hindus, Babylonians, Persians, Romans, Chinese, Greeks, and Yankee civilizations used it primarily for ritual, embalming, and for its incense in cultural functions. This plant is mentioned in ancient Unani texts as an efficient remedy for respiratory disease, asthma, cough, vessel diseases, diarrhea, dysentery, ringworm, boils, fevers (antipyretic), skin, and blood diseases, mouth sores, channel discharges, etc. The qualitative phytochemical examination of plant extract indicates the presence of tannic acid, pentosans, lignin, holocellulose, β-sitosterol, volatile (cadinene, eleneol, gereniol, linalool, β-pinene, phenols, terpenyl acetate, bornyl acetate, etc.) and non-volatile (diterpene alcohol serratol, α-amyrin, and β-amyrin, triterpenic acids viz., boswellic acid) oils. It primarily possesses anti-arthritic, medicine, anti-hyperlipidemic, anti-cancer, hypoglycemic, anti-asthmatic, analgesic, hepatoprotective, etc. pharmacological activities.

Chronic inflammation is a key culprit factor in the onset and progression of several diseases. Novel and pharmacologically effective therapeutic approaches are needed for new treatment remedy or improved pharmacokinetics and pharmacodynamics for existing synthetic drugs, in particular natural products. Boswellic acids are well-known natural products, with capacity to effectively retard inflammation without severe adverse effects. However, the therapeutic use of Boswellic acids are greatly hindered by its poor pharmacokinetic properties. Co-administration strategies that facilitate the oral absorption and distribution of Boswellic acids should lead to a safe and more effective use of this product prophylactically and therapeutically in inflammatory disorders. In this study, we examined the effect of Piper longum extract on the absorption and bioavailability of Boswellic acid in rabbits. In addition, we further explored computational pharmacodynamic interactions between Piper longum and Boswellic acid. Piper longum extract at 2.5 and 10 mg/kg, increased the bioavailability of Boswellic acid (p < 0.05). Based on our drug-based computational modeling, cytochrome P450 (CYP450)-mediated mechanism was involved in increased bioavailability. These findings confirmed that Piper longum with Boswellic acid may be administered orally together for effective therapeutic efficacy. Thus, our studies support the application of Piper longum with Boswellic acid as a novel therapeutic avenue in diseases associated with inflammation.

Estrogen is instrumental in the pathological process of osteoporosis because a deficiency of this hormone increases the release of bone-resorbing cytokines. Acetyl-11-keto-&beta, boswellic acid (AKBA), a constituent from Boswellia serrata, has an anti-inflammatory effect by inhibiting tumor necrosis factor-&alpha, (TNF-&alpha, ) expression, which leads to a decline in receptor activator of nuclear factor-kappa B (NF-&kappa, B) ligand, and consequently, a reduction in osteoclast activity. Hence, AKBA may be beneficial against bone loss during osteoporosis. Therefore, the current study intended to evaluate the beneficial effects of AKBA in ovariectomy-induced osteoporosis and to investigate its mechanism of action. Sham-operation or ovariectomy female Sprague Dawley rats were used for evaluating the antiosteoporotic effect of AKBA in this study. AKBA (35 mg/kg, p.o.) and estradiol (0.05 mg/kg, i.m.) were administered for 42 days. At the end of the experiment, body and uterus weights, serum and urine calcium and phosphorus, serum alkaline phosphatase, and urinary creatinine levels, besides serum levels of NF-&kappa, B and TNF-&alpha, were determined. Weight, length, thickness, hardness, calcium content, as well as the bone mineral density of femur bone and lumbar vertebra were measured. A histopathological examination was also carried out. AKBA ameliorated all tested parameters and restored a normal histological structure. Thus, AKBA showed good antiosteoporotic activity, which may be mediated through its suppression of the NF-&kappa, B-induced TNF-&alpha, signaling pathway.

Aims Testicular torsion/detorsion (T/D) is a critical medical condition that necessitates prompt surgical intervention to avoid testicular atrophy and infertility. The use of natural compounds may protect against the associated detrimental oxidative stress and inflammatory responses. Interestingly, acetyl-11-keto-β-boswellic acid (AKBA), the main active constituent of Boswellia resin, has shown potent inhibitory effect on 5-lipoxygenase enzyme which converts arachidonic acid into inflammatory mediators. Therefore, this study was conducted to assess the protective mechanisms by which AKBA may protect against testicular T/D injury in rats. Main methods Male rats were randomly distributed into five groups: Sham, AKBA (50 mg/kg, p.o.), unilateral testicular T/D, AKBA at two dose levels (25 or 50 mg/kg for 15 successive days) followed by T/D. Histological examination and Johnsen's score were performed to assess testicular injury and perturbations in spermatogenesis. Biochemical parameters included markers of testicular function (serum testosterone), oxidant/antioxidant status (malondialdehyde, glutathione), inflammation (5-lipoxygenase, leukotriene-B4, myeloperoxidase, interleukin-1β, interleukin-6), apoptosis (Bax, Bcl2, caspase-3), DNA integrity (quantitative DNA fragmentation, DNA laddering, PARP-1), energy production (ATP), in addition to p38 MAPK and JNK protein expression. Key findings In a dose dependent manner, AKBA significantly inhibited testicular T/D-induced upregulation of 5-LOX/LTB4 and p38-MAPK/JNK/Bax pathways and their associated downstream inflammatory and apoptotic cascades. These effects were accompanied with ATP replenishment and DNA preservation, resulting ultimately in salvage of the testis. Significance Unprecedentedly, the present mechanistic study revealed the pathways by which AKBA may inhibit testicular T/D injury and offered a novel protective approach that may attenuate the severity of this condition.

The foremost neurodegenerative disease is Alzheimer's (AD), which is characterized as a gradual decrease in memory, cognitive function, and also personal changes occurred. This study aims to assess the role of boswellic bioactive component in control Alzheimer's disease through enhancing mitochondrial electron transport chain complexes in the rat model. Rats were divided into five equal groups: the control group (G1), boswellic acid control group (G2), AD disease group (G3), boswellic acid -pre-treated group (G4) and boswellic acid-treated group (G5). At the end of the experiment, blood glucose level, tau protein, different neurochemicals parameters (dopamine, acetylcholine), L-malondialdehyde (MDA) levels, and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities was determined. Also, GLUT2 and mitochondrial electron transport chain complexes were evaluated. As a result, an increase in hippocampus glucose, tau protein expression, MDA and GLUT2 in the AD group (G3) compared to control groups (G1 and G2) has been recorded. These parameters were declined after pre (G4) and treated (G5) by boswellic acid. The neurochemicals, antioxidants parameters, four mitochondrial chain complexes activities and their gene expression in the hippocampus of the AD group were decreased compared to the control groups (G1 and G2). In contrast, pre and treated groups by boswellic acid (G4 and G5, respectively) have shown an increase in antioxidants parameters, and the activities of four mitochondrial complexes, with the best improvement in the pre-treated group (G4), then treated group (G5). In conclusion; the boswellic acid improved the antioxidant and mitochondrial complexes in Alzheimer's disease.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Current therapeutic strategies are based on the use of Temozolomide (TMZ) and antihuman epidermal growth factor receptor (EGFR) drugs, such as Afatinib. However, clinically relevant drug-resistance events are still present and closely related to a proinflammatory cancer brain microenvironment. The primary aim of this study is the association of Boswellic acid (BA), a molecule derived from Boswellia Serrata, with TMZ and Afatinibin different human GBM cells. We performed cell viability studies evaluating its antioxidant and anti-inflammatory effects analyzing p65/NF-κB and Leukotriene B4 expression and production of interleukins and growth factors (IL-8, IL-6, vascular endothelial growth factor, CXCL-12, and MMP-9). Considering the cardiotoxicity of TMZ and anti-EGFR drugs, we evaluated the putative cardioprotective effects of BA in adult cardiomyocytes. BA significantly increased the anticancer activities of TMZ and Afatinib. These effects are related to its anti-inflammatory and antioxidant effects, based on the inhibition of growth factors and proinflammatory interleukins. Notably, BA exerts also cardioprotective effects in combination to both drugs. This study provides evidences of anti-inflammatory, cardioprotective, and chemo sensitizing effects of BA in glioblastoma cells giving a rationale for new translational studies based on the use of this natural molecule during conventional therapies. Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Current therapeutic strategies are based on the use of Temozolomide (TMZ) and antihuman epidermal growth factor receptor (EGFR) drugs, such as Afatinib. However, clinically relevant drug-resistance events are still present and closely related to a proinflammatory cancer brain microenvironment. The primary aim of this study is the association of Boswellic acid (BA), a molecule derived from Boswellia Serrata, with TMZ and Afatinibin different human GBM cells. We performed cell viability studies evaluating its antioxidant and anti-inflammatory effects analyzing p65/NF-B and Leukotriene B4 expression and production of interleukins and growth factors (IL-8, IL-6, vascular endothelial growth factor, CXCL-12, and MMP-9). Considering the cardiotoxicity of TMZ and anti-EGFR drugs, we evaluated the putative cardioprotective effects of BA in adult cardiomyocytes. BA significantly increased the anticancer activities of TMZ and Afatinib. These effects are related to its anti-inflammatory and antioxidant effects, based on the inhibition of growth factors and proinflammatory interleukins. Notably, BA exerts also cardioprotective effects in combination to both drugs. This study provides evidences of anti-inflammatory, cardioprotective, and chemo sensitizing effects of BA in glioblastoma cells giving a rationale for new translational studies based on the use of this natural molecule during conventional therapies.

Acetyl 11 keto β boswellic acid (AKBA) is anti-inflammatory agent obtained from oleoresin gum of Boswellia serrata. In the present study microwave assisted extraction (MAE) technique has been employed for extraction AKBA. Firstly MAE was optimized using one factor at a time approach by selecting different parameters such as solvents type, microwave power (W), extraction time (min), solute to solvent ratio (w/v), ethanol concentration (%) and number of extraction cycle. MAE of AKBA was further optimized using orthogonal array design (OAD). OAD is a statistical tool used to optimize MAE process as well as to determine significant parameter that influences the extraction yield of AKBA. Optimized conditions for OAD were found as microwave power of 272 W, extraction time of 4 min (30 sec on/off), solute to solvent ratio of 1:25 (w/v) and ethanol concentration of 90% (v/v) for highest 92.00 ± 0.25 mg/g extraction yield of AKBA in one extraction cycle. Microwave power (W) has shown significant influence ...

Boswellic acids (BAs) are a group of pentacyclic triterpenes present in gum-resin of Boswellia serrata . They are well known for their anti-inflammatory, hypolipidemic, immunomodulatory and anti-tumor activity, but they have poor aqueous solubility and limited bioavailability. In order to enhance their aqueous solubility, inclusion complexes of BAs with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) were synthesized and their drug release profiles were studied. Molecular associations of β-CD and HP-β-CD with BAs were investigated by phase solubility studies. The stability constants were found to be 380.2 and 145.9 M -1 for BA: β-CD and BA: HP-β-CD inclusion complexes, respectively with A N - type curve. BA: β-CD and BA: HP-β-CD inclusion complexes were synthesized using kneading (KN), co-precipitation (CP) and solvent evaporation (SE) methods in 1:1 as well as 1:2 ratios. Further these were characterized by Fourier transform infrared (FTIR) spectrophotometry, Powder X-ray Diffraction (P-XRD) and Differential scanning calorimetric (DSC) analysis. FTIR analysis showed shifting of frequencies in complexes as compared to CDs and BAs. P-XRD data obtained for BA: β-CD complexes synthesized by CP and SE methods showed amorphous pattern. Also, DSC analysis showed a change in thermal behaviour for synthesized complexes. In vitro drug release studies of BA: β-CD complexes showed enhanced release with 1:2 complexes than 1:1 complexes at pH 1.2 and pH 6.8. Similarly, drug release enhancement was observed more with BA: HP-β-CD complexes in 1:2 ratio than 1:1. To understand the interaction of BAs with CD cavity molecular modelling studies were performed which favored 1:2 complex formation over 1:1 complexes. The study thus highlights that CDs can be used for solubility and dissolution enhancement of BAs.

Boswellia serrate gum resin extract is a potent anti-inflammatory agent that is widely used in ancient and modern medicinal systems. However, the efficacy of this bioactive ingredient is questionable due to its poor oral bioavailability. In this work, self-nanoemulsifying system (SNES) was used to enhance the systemic concentration of boswellic acids. The systemic concentrations of 11-keto-β-boswellic acid (KBA) and acetyl-11-keto-β-boswellic acid (AKBA), the most bioactive components of boswellic acids, were used as indicators to evaluate the efficiency of self-emulsifying system. In the study of lipolysis, the aqueous solubility and bioaccessibility of KBA and AKBA were increased by 2.7 and 2.3 folds, respectively. From the in vivo pharmacokinetic study, SNES triggered a significant increase in the oral bioavailability of KBA and AKBA by 2.2 and 2.0 times higher than the bulk oil suspension, respectively. Therefore, SNES with superior storage stability is an effective oral formulation to enhance bioavailability of boswellic acids.

Acetyl 11 keto β boswellic acid (AKBA), a potent anti-inflammatory agent obtained from Boswellia serrata oleogum resin, is mostly used for the treatment of various chronic inflammatory diseases. Ethanol modified supercritical fluid extraction (SFE) was employed to extract AKBA from Boswellia serrata. The optimal conditions for AKBA extraction were determined by Box–Behnken design which was employed to estimate the effect of three independent variables (pressure, extraction time and temperature) on the AKBA yield. The interactions between pressure with temperature and extraction time were found to be significant (p

Malaria eradication is still a major global health problem in developing countries, which has been of more concern ever since the malaria parasite has developed resistance against frontline antimalarial drugs. Historical evidence proves that the plants possess a major resource for the development of novel anti-malarial drugs. In the present study, the bioactivity guided fractionation of the oleogum-resin of Boswellia serrata Roxb. yielded the optimum activity in the ethyl acetate fraction with an IC50 of 22 ± 3.9 μg/mL and 26.5 ± 4.5 μg/mL against chloroquine sensitive (NF54) and resistant (K1) strains of Plasmodium falciparum respectively. Further, upon fractionation, the ethyl acetate fraction yielded four major compounds, of which 3-Hydroxy-11-keto-β-boswellic acid (KBA) was found to be the most potent with IC50 values 4.5 ± 0.60 µg/mL and 6.25 ± 1.02 μg/mL against sensitive and resistant strains respectively. KBA was found to inhibit heme detoxification pathways, one of the most common therapeutic targets, which probably lead to an increase in reactive oxygen species (ROS) and nitric oxide (NO) detrimental to P. falciparum. Further, the induced intracellular oxidative stress affected the macromolecules in terms of DNA damage, increased lipid peroxidation, protein carbonylation as well as loss of mitochondrial membrane potential. However, it did not exhibit any cytotoxic effect in VERO cells. Under in vivo conditions, KBA exhibited a significant reduction in parasitemia, retarding the development of anaemia, resulting in an enhancement of the mean survival time in Plasmodium yoelii nigeriensis (chloroquine-resistant) infected mice. Further, KBA did not exhibit any abnormality in serum biochemistry of animals that underwent acute oral toxicity studies at 2000 mg/kg body weight.

The oleo gum resin of Boswellia serrata belonging to family Burseraceae, is Ayurvedic medicine and has been used for the treatment of inflammatory diseases and arthritic diseases in many countries. Acetyl 11-keto-β-boswellic acid (AKBA) is a potent anti-inflammatory agent obtained from oleo gum resin of Boswellic serrata. Our aim is to extract maximum amount of AKBA from Boswellic serrata by using Three Phase Partitioning (TPP) technique. In the TPP system, the effect of different process parameters such as ammonium sulfate concentration, extraction time, slurry to t-butanol ratio, solute to t-butanol ratio, pH and temperature, was studied in order to enhance the extraction of AKBA. Under the optimized conditions of ammonium sulfate concentration 0–50% (w/v), extraction time 180 min, slurry to t-butanol ratio 1:1 (v/v), solute to solvent ratio 1:25 (w/v), pH 6 and temperature 50 °C, the maximum yield of AKBA was found to be (80 ± 0.33 mg/g). TPP technique gave higher extraction yield of AKBA compared to conventional Soxhlet extraction (18 ± 0.37 mg/g), batch extraction (20 ± 0.45 mg/g), ultrasound assisted extraction (UAE) (24.23 ± 0.28 mg/g). Thus, TPP can be recommended as an attractive and simple technique for the extraction of AKBA from Boswellic serrata.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) that can cause cognition, mobility, and sensory impairments. It is considered one of the most common non-traumatic causes of disability in the world. The aim of the present article was to review the clinical evidence related to medicinal plants in the management of MS symptoms. Electronic databases, including the Cochrane Library, Pubmed, and Scopus, were searched for entries from 1966 to February 2017. Only clinical studies were included in this review. Different medicinal plants have positive effects on MS, including Andrographis paniculata, Boswellia papyrifera, Ruta graveolens, Vaccinium spp., Camellia sinensis, Panax ginseng, Aloysia citrodora, Ginkgo biloba, Oenothera biennis, and Cannabis sativa. C. sativa had the highest level of clinical evidence, supporting its efficacy in MS symptoms. Proanthocyanidins, ginkgo flavone glycosides, ginsenosides, epigallocatechin-3-gallate, cannabinoids (including delta-9-tetrahydrocannabinol and cannabidiol), boswellic acid, and andrographolide were presented as the main bioactive components of medicinal plants with therapeutic benefits in MS. The main complications of MS in which natural drugs were effective include spasticity, fatigue, scotoma, incontinence, urinary urgency, nocturia, memory performance, functional performance, and tremor. Herbal medicines were mostly well tolerated, and the adverse effects were limited to mild to moderate. Further well-designed human studies with a large sample size and longer follow-up period are recommended to confirm the role of medicinal plants and their metabolites in the management of MS.

Testing and screening of plant-derived molecules on normal human cells in vitro is a widely used approach for discovering their eventual health beneficial effects for human ageing and longevity. As little is known about age-associated differential effects of such molecules, here we report that young (&lt, 25% replicative lifespan completed) and near-senescent (&gt, 90% replicative lifespan completed) human skin fibroblasts exposed for 1&ndash, 15 days to a wide range of concentrations (0.1&ndash, 100 &mu, M) of the three selected phytochemicals, namely &alpha, boswellic acid acetate (ABC), praeruptorin-A (PTA), and salvianolic acid-B (SAB) had age-related differential effects. The parameters studied were the metabolic activity (MTT assay), cellular morphological phenotype, one-step growth characteristics, expression of genes involved in the cell cycle regulation and cytokine network genes, protein levels of p53, cytosolic superoxide dismutase (SOD1) and microtubule-associated protein 1A/1B-light chain 3 (LC3), and the extent of protein carbonylation and protein aggregation as a sign of oxidative stress. All three compounds showed biphasic hormetic dose response by stimulating cell growth, survival and metabolic activity at low doses (up to 1 &mu, M), while showing inhibitory effects at high doses (&gt, 10 &mu, M). Furthermore, the response of early passage young cells was different from that of the late passage near-senescent cells, especially with respect to the expression of cell cycle-related and inflammation-related genes. Such studies have importance with respect to the use of low doses of such molecules as health-promoting and/or ageing-interventions through the phenomenon of hormesis.

Traditionally, the gum resin produced from the Boswellia serrata plant has been used in as a therapeutical compound. The gum that contains a chemical known as boswellic acid, AKBA (3-O-acetyl-11 keto-β-boswellic acid), and widely in ayurvedic medicines. This is used to treat the disease like reduction in various inflammatory conditions of the skin, eye, as well as respiratory disorders such as asthma, bronchitis, and laryngitis. The boswellic acids were also found capable to inhibit both hemolysis and chemotaxis of leukocytes and were shown to work by inhibiting C3-convertase, a key enzyme of the classical complementary pathway. In addition to this, the compound shows beneficial effects in various pharmacological properties like immunomodulation activity, polyarthritis, activity against Hepatitis C-virus and other harmful microbes, Colitis and Crohn's disease, and so on. The boswellic acid is also used to treat patients with memory disorders. In this chapter, the chemical nature and isolation of boswellic acid and its therapeutic importance have been highlighted.

Alzheimer's disease (AD) is a complex disease involved oxidative stress and inflammation in its pathogenesis. Acetyl-11-keto-β-boswellic acid (AKBA) is an active triterpenoid compound from extracts of Boswellia serrata, which has been widely used as an antioxidant and anti-inflammatory agent. The present study was to determine whether AKBA, a novel candidate, could protect against cognitive and neuropathological impairments in AD. We found that AKBA treatment resulted in a significant improvement of learning and memory deficits, a dramatic decrease in cerebral amyloid-β (Aβ) levels and plaque burden, a profound alleviation in oxidative stress and inflammation, and a marked reduction in activated glial cells and synaptic defects in the APPswe/PS1dE9 mice. Furthermore, amyloid precursor protein (APP) processing was remarkably suppressed with AKBA treatment by inhibiting beta-site APP cleaving enzyme 1 (BACE1) protein expression to produce Aβ in the APPswe/PS1dE9 mice brains. Mechanistically, AKBA modulated antioxidant and anti-inflammatory pathways via increasing nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression, and via declining phosphorylation of inhibitor of nuclear factor-kappa B alpha (IκBα) and p65. Collectively, our findings provide evidence that AKBA protects neurons against oxidative stress and inflammation in AD, and this neuroprotective effect involves the Nrf2/HO-1 and nuclear factor-kappa B (NF-κB) signaling pathways.

BACKGROUND Some substances of plant origin have been reported to exert an effect in reducing intestinal neoplasm development, especially in animal models. Adenomatous polyposis coli multiple intestinal neoplasia - ApcMin/+ is the most studied murine model of genetic intestinal carcinogenesis. AIM To assess whether an enriched nutritional formulation (silymarin, boswellic acid and curcumin) with proven "in vitro" and "in vivo" anti-carcinogenetic properties may prevent inherited intestinal cancer in animal model. METHODS Forty adenomatous polyposis coli multiple intestinal neoplasia - ApcMin/+ mice were used for the study of cancer prevention. They were divided into two groups: 20 assumed standard and 20 enriched diet. At the 110th d animals were sacrificed. In each group, four subgroups received intraperitoneal bromodeoxyuridine injection at different times (24, 48, 72 and 96 h before the sacrifice) in order to assess epithelial turnover. Moreover, we evaluated the following parameters: Intestinal polypoid lesion number and size on autoptic tissue, dysplasia and neoplasia areas by histological examination of the whole small intestine, inflammation by histology and cytokine mRNA expression by real-time polymerase chain reaction, bromodeoxyuridine and TUNEL immuno-fluorescence for epithelial turnover and apoptosis, respectively. Additionally, we performed western blotting analysis for the expression of estrogen alpha and beta receptors, cyclin D1 and cleaved caspase 3 in normal and polypoid tissues. RESULTS Compared to standard, enriched diet reduced the total number (203 vs 416) and the mean ± SD/animal (12.6 ± 5.0 vs 26.0 ± 8.8; P < 0.001) of polypoid lesions. In enriched diet group a reduction in polyp size was observed (P < 0.001). Histological inflammation and pro-inflammatory cytokine expression were similar in both groups. Areas of low-grade dysplasia (P < 0.001) and intestinal carcinoma (IC; P < 0.001) were significantly decreased in enriched diet group. IC was observed in 100% in standard and 85% in enriched formulation assuming animals. Enriched diet showed a faster epithelial migration and an increased apoptosis in normal mucosa and low-grade dysplasia areas (P < 0.001). At western blotting, estrogen receptor beta protein was well expressed in normal mucosa of enriched and standard groups, with a more marked trend associated to the first one. Estrogen receptor alpha was similarly expressed in normal and polypoid mucosa of standard and enriched diet group. Cleaved caspase 3 showed in normal mucosa a stronger signal in enriched than in standard diet. Cyclin D1 was more expressed in standard than enriched diet group of both normal and polypoid tissue. CONCLUSION Our results are suggestive of a chemo-preventive synergic effect of the components (silymarin, boswellic acid and curcumin) of an enriched formulation in inherited IC. This effect may be mediated by the reduction of epithelial proliferation, the increase of apoptosis and the acceleration of villous cell renewal due to dietary formulation intake.

Frankincense and myrrha (FM), commonly used as a classical herbal pair, have a wide range of clinical applications and definite anti-inflammatory activity. However, anti-neuroinflammation effects and mechanisms are not clear. In this study, we adopted a lipopolysaccharide (LPS)-induced microglial (BV2) cell model and a network pharmacology method to reveal the anti-neuroinflammatory effects and mechanisms of boswellic acid (BA) and myrrha sesquiterpenes (MS) with different proportions of compatibility. The data showed that the different ratios of BA and MS had different degrees of inhibition of interleukin-1&beta, (IL-1&beta, ), IL-6, and inducible nitric oxide synthase (iNOS) mRNA expression, down-regulated the phosphor-nuclear factor kappa B/nuclear factor kappa B (p-NF-ҡB)/(NF-ҡB), phosphorylated protein kinase b/protein kinase b (p-AKT/AKT), and Toll-like receptor 4 (TLR4) protein expression levels, and increased phospho-PI3 kinase (p-PI3K) protein expression levels. When the ratios of BA and MS were 10:1, 5:1, and 20:1, better effective efficacy was exhibited. According to the correlation analysis between the effect index and bioactive substances, it was suggested that 2-methoxy-5-acetoxy -fruranogermacr-1(10)-en-6-one (Compound 1), 3&alpha, acetyloxylanosta-8,24-dien-21-oic acid (Compound 2), 11-keto-boswellic acid (Compound 3), and 3-acetyl-11-keto-&beta, boswellic acid (Compound 4) made important contributions to the treatment of neuroinflammation. Furthermore, based on the network pharmacological analysis, it was found that these four active compounds acted on 31 targets related to neuroinflammation and were involved in 32 signaling pathways which mainly related to the immune system, cardiovascular system, and nervous system, suggesting that BA and MS could be used to treat neuroinflammation.

Acetyl-11-keto-β-boswellic acid (AKBA), a triterpenoid from Boswellia serrate, is regarded as an angiogenesis inhibitor. However, its toxicity is unknown. The aim of this study was to examine its d...

For centuries, frankincense extracts have been commonly used in traditional medicine, and more recently, in complementary medicine. Therefore, frankincense constituents such as boswellic and lupeolic acids are of considerable therapeutic interest. Sixteen frankincense nutraceuticals were characterized by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), revealing major differences in boswellic and lupeolic acid compositions and total contents, which varied from 0.4% to 35.7%. Frankincense nutraceuticals significantly inhibited the release of proinflammatory cytokines, such as TNF-&alpha, IL-6, and IL-8, by LPS-stimulated peripheral blood mononuclear cells (PBMC) and whole blood. Moreover, boswellic and lupeolic acid contents correlated with TNF-&alpha, IL-1&beta, IL-6, IL-8, and IL-10 inhibition. The nutraceuticals also exhibited toxicity against the human triple-negative breast cancer cell lines MDA-MB-231, MDA-MB-453, and CAL-51 in vitro. Nutraceuticals with total contents of boswellic and lupeolic acids &gt, 30% were the most active ones against MDA-MB-231 with a half maximal inhibitory concentration (IC50) &le, 7.0 &micro, g/mL. Moreover, a frankincense nutraceutical inhibited tumor growth and induced apoptosis in vivo in breast cancer xenografts grown on the chick chorioallantoic membrane (CAM). Among eight different boswellic and lupeolic acids tested, &beta, ABA exhibited the highest cytotoxicity against MDA-MB-231 with an IC50 = 5.9 &micro, M, inhibited growth of cancer xenografts in vivo, and released proinflammatory cytokines. Its content in nutraceuticals correlated strongly with TNF-, IL-6, and IL-8 release inhibition.

This study is to investigate the protective effect of Acetyl-α-boswellic acid and Acetyl-β-boswellic mixture(α/β-ABA), which is the active ingredients isolated from Frankincense, on actue pancreatitis and its mechanism. Our experimental results showed that 2 μM α/β-ABA reduced production of NO, TNF-α, IL-6, IL-10 and IL-1β in RAW264.7 cells that were stimulated with lipopolysaccharide (LPS) which indicates its anti-inflammatory role. In pancreatitis model induced by caerulein, intra-gastrical administration of 100 mg/kg α/β-ABA relieved inflammatory cells infiltration significantly and attenuated the serum elevation of amylase TNF-α and IL-6 remarkably in mice. Furthermore, α/β-ABA down-regulated mitogen-activated protein kinase (MAPK) family phosphorylated proteins in pancreas, including phosphorylated p38, ERK1/2 and JNK, to reduce the serum inflammatory factors. Finally, α/β-ABA alleviated the pancreatic edema and inflammatory cell infiltration in pancreatitis mice model. This study suggests that α/β-ABA may be targeted for drug development against pancreatitis via modulating MAPKs pathway.

Natural compounds, in recent years, have attracted significant attention for their use in the prevention and treatment of diverse chronic diseases as they are devoid of major toxicities. Boswellic acid (BA), a series of pentacyclic triterpene molecules, is isolated from the gum resin of Boswellia serrata and Boswellia carteri. It proved to be one such agent that has exhibited efficacy against various chronic diseases like arthritis, diabetes, asthma, cancer, inflammatory bowel disease, Parkinson’s disease, Alzheimer’s, etc. The molecular targets attributed to its wide range of biological activities include transcription factors, kinases, enzymes, receptors, growth factors, etc. The present review is an attempt to demonstrate the diverse pharmacological uses of BA, along with its underlying molecular mechanism of action against different ailments. Further, this review also discusses the roadblocks associated with the pharmacokinetics and bioavailability of this promising compound and strategies to overcome those limitations for developing it as an effective drug for the clinical management of chronic diseases.

Background Osteoarthritis is a common canine disease frequently treated with nutritional supplements that often lack independent verification of ingredients, active ingredient concentration, efficacy, or safety. Human supplements containing Boswellia serrata extracts (BSE) with high concentrations of active constituents 3-acetyl-11-keto-β-boswellic acid (AKBA) and 11-keto-β-boswellic acid (KBA) are bioavailable, safe, and efficacious in the alleviation of symptoms of naturally occurring osteoarthritis in people. Thus, oral AKBA and/or KBA supplementation could be a promising novel therapy for dogs with osteoarthritis. The primary objective of this study was to determine the concentrations of AKBA and KBA within six human and seven canine market formulations containing BSE administered to dogs, using a derivation of the previously validated high performance liquid chromatography (HPLC) method. The secondary objective was to compare measured concentrations to label claims. Results The mean concentrations of AKBA and KBA within the formulations tested were 42.3 mg/g AF (0.1–155.7 mg/g AF) and 5.2 mg/g AF (0–24.8 mg/g AF), respectively, with four of the formulations containing an undetectable amount of KBA. None of the market formulations had a label claim for KBA. For the five tested formulations with a label claim for AKBA, the mean percentage of detected AKBA was 173% of the concentration listed on the label (range: 114–224%). Formulations claiming to contain AKBA had a mean AKBA concentration of 98.2 mg/g AF, significantly higher than formulations claiming only to contain BSE (7.4 mg/g AF; p = 0.01). Conclusions This study demonstrated a large variation of boswellic acid concentrations in market formulations claiming to contain BSE, with products claiming to contain AKBA containing higher concentrations of AKBA than other products. There was also a large variation in, and overall high, percent difference between label claims and measured concentrations of AKBA. All products met or exceeded label claims. However, differences between label amounts and detected concentrations confirm the need for independent laboratories to quantify concentrations of active ingredients in supplements containing BSE. This would be necessary prior to the use of these formulations in the research or clinical setting.

The 5-lipoxygenase enzyme is a proinflammatory enzyme and produces leukotrienes. Evidence has shown that inflammation contributes to Alzheimer’s disease. On the other hand, boswellic acid derivatives have also been shown to be involved in Alzheimer’s disease. In this study, the interaction of four different derivatives of boswellic acid with 5-lipoxygenase enzyme was investigated using molecular dynamics simulation. The simulation of the enzyme was also carried out alone. Calculation of Cα-RMSD indicates that the enzyme stability is slightly affected by boswellic acid derivatives. Calculating the radius of gyration of the enzyme also shows that the overall shape of the protein is not affected by ligands. The RMSF values of the enzyme residues were calculated in the presence of boswellic acid derivatives and it was compared with that in the absence of ligands. The results show that the flexibility of the enzyme residues is influenced by ligands. The residues, whose flexibility is reduced, are scattered throughout the enzyme. However, their number is great in the N-terminal residue. The binding affinity between boswellic acid derivatives and the enzyme residues was calculated using the measure of conformation factor. The results show that the residues interacting with ligands are in the area of the first domain of enzyme. The results obtained from molecular dynamics simulation are well-consistent with the experimental evidence related to the inhibitory effect of the mentioned compounds with 5-lipoxygenase.

A series of new 11-keto-β-boswellic acid were partially-synthesized by modifying the hydroxyl and carboxylic acid functional groups of ring A. The structures of the new analogs were confirmed by detailed spectral data analysis. Compounds

Frankincense is an oleogum resin from Boswellia trees of the Burseraceae family. The oleogum resin contains 15–20 % triterpenic acids, including therapeutically active boswellic acids [1]. Extracts...