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Biological activity of Boswellia extract (BE) has been attributed to its main active ingredients; i.e. Boswellic acids (BAs). BE/BAs possess a promising therapeutic potential in neurodegenerative disorders; including Alzheimer's disease (AD). The multifactorial nature of AD pathophysiology necessitates the development of the disease-modifying agents (DMA). Recent multi-targeting approaches for the DMAs development have brought more attention to the plant-derived compounds regarding their better human compatibility because of their biologic origin. This review addresses the current knowledge on the anti-AD activity of BE/BAs based on the available in silico, in vitro, in vivo studies and clinical trials. The contribution of BE/BAs in inflammatory pathways, Tau and β-amyloid proteins, microtubule functions, oxidative stress, cholinesterase and diabetes/insulin pathways involved in AD have been discussed. BAs efficacy in different AD-related pathways has been confirmed in vitro and in vivo. They can be considered as valuable scaffold/lead compounds for multi-targeted DMAs in anti-AD drug discovery and development.

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.

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

Medicinal plants represent a big reservoir for discovering new drugs against all kinds of diseases including inflammation. In spite the large number of promising anti-inflammatory plant extracts and isolated components, research on medicinal plants proves to be very difficult. Based on that background this review aims to provide a summarized insight into the hitherto known pharmacologically active concentrations, bioavailability, and clinical efficacy of boswellic acids, curcumin, quercetin and resveratrol. These examples have in common that the achieved plasma concentrations were found to be often far below the determined IC50 values in vitro. On the other hand demonstrated therapeutic effects suggest a necessity of rethinking our pharmacokinetic understanding. In this light this review discusses the value of plasma levels as pharmacokinetic surrogates in comparison to the more informative value of tissue concentrations. Furthermore the need for new methodological approaches is addressed like the application of combinatorial approaches for identifying and pharmacokinetic investigations of active multi-components. Also the physiological relevance of exemplary in vitro assays and absorption studies in cell-line based models is discussed. All these topics should be ideally considered to avoid inaccurate predictions for the efficacy of herbal components in vivo and to unlock the “black box” of herbal mixtures.

Boswellia sacra oleo gum resin (Burseraceae) commonly known as frankincense is traditionally used in many countries for its beneficial effect on male fertility. This study explores its effect on the male reproductive system after a 60-day repeated administration at two different doses to rats (in vivo) and on human Leydig cells (in vitro). The methanolic extract of B. sacra was analyzed for the presence of various constituents by preliminary phytochemical analysis and gas chromatography-mass spectrometry (GC-MS) while quantitative analysis of boswellic acids was done by high-performance liquid chromatography (HPLC). Administration of B. sacra extract to rats elevated the serum testosterone levels with an associated reduction in serum levels of FSH and LH. An increase in the activity of antioxidant enzymes, superoxide dismutase and catalase, was seen. A dose-dependent increase in the sperm count and sperm motility was also observed. The in vivo results were supported by changes in the expression of the Bcl-2 gene and caspase-3 gene in human Leydig cells in vitro. The results of this study support the traditional use of B. sacra to increase male fertility.

Boswellic acids (BAs) have been shown to possess antiviral activity. Using bioinformatic methods, it was tested whether or not acetyl‐11‐keto‐β‐boswellic acid (AKBA), 11‐keto‐β‐boswellic acid (KBA), β‐boswellic acid (BBA), and the phosphorylated active metabolite of Remdesivir® (RGS‐P3) bind to functional proteins of SARS‐CoV‐2, that is, the replicase polyprotein P0DTD1, the spike glycoprotein P0DTC2, and the nucleoprotein P0DTC9. Using P0DTD1, AKBA and KBA showed micromolar binding affinity to the RNA‐dependent RNA polymerase (RdRp) and to the main proteinase complex Mpro. Phosphorylated BAs even bond in the nanomolar range. Due to their positive and negative charges, BAs and RGS‐P3 bond to corresponding negative and positive areas of the protein. BAs and RGS‐P3 docked in the tunnel‐like cavity of RdRp. BAs also docked into the elongated surface rim of viral Mpro. In both cases, binding occurred with active site amino acids in the lower micromolecular to upper nanomolar range. KBA, BBA, and RGS‐P3 also bond to P0DTC2 and P0DTC9. The binding energies for BAs were in the range of −5.8 to −6.3 kcal/mol. RGS‐P3 and BAs occluded the centrally located pore of the donut‐like protein structure of P0DTC9 and, in the case of P0DTC2, RGS‐P3 and BAs impacted the double‐wing‐like protein structure. The data of this bioinformatics study clearly show that BAs bind to three functional proteins of the SARS‐CoV‐2 virus responsible for adhesion and replication, as does RGS‐P3, a drug on the market to treat this disease. The binding effectiveness of BAs can be increased through phosphate esterification. Whether or not BAs are druggable against the SARS‐CoV‐2 disease remains to be established., Bioinformatic methods showed that acetyl‐11‐keto‐β‐boswellic acid, 11‐keto‐β‐boswellic acid, β‐boswellic acid, and the phosphorylated active metabolite of Remdesivir® bind to functional proteins of SARS‐CoV‐2: the replicase polyprotein P0DTD1, the spike glycoprotein P0DTC2, and the nucleoprotein P0DTC9. The binding effectiveness of the boswellic acids can be increased through phosphate esterification.

Boswellic acids (BAs) are the main bioactive compounds of frankincense, a natural resin obtained from the genus Boswellia. This study aimed to develop a self-nanoemulsifying delivery system (SNEDS) to improve the antimicrobial and antiproliferative activities of standardized frankincense extract (Fr-extract). Fr-extract was standardized, and BA content was quantified using the developed HPLC-UV method. Screening studies of excipients followed by formula optimization using a mixture simplex lattice design was employed. The optimized Fr-SENDS formulation was characterized. Furthermore, microbiological and antiproliferative assessments of the standardized Fr-extract and Fr-SNEDS were evaluated. Quantification demonstrated that the major constituent is 11-keto-boswellic acid (KBA) (16.25%) among BA content (44.96%). The optimized Fr-SENDS (composed of 5% CapryolTM 90, 48.7% Gelucire® 44/14 and 46.3% ethanol) showed spherical nanosized dispersions with DS, PDI, and zeta potential of 17.9 nm, 0.2, and −14.5 mV, respectively. Fr-SNEDS exhibited lower MIC and MBC values compared with Fr-extract against pathogens conjugated with lung cancer and was comparable to reference antimicrobials. Fr-SNEDS showed superior antiproliferative activity over Fr-extract, with IC50 values of 20.49 and 109.5 μg mL−1, respectively. In conclusion, the optimized Fr-SNEDS could be easily developed and manufactured at a low cost and the in vitro results support its use as a potential adjuvant oral therapy for lung cancer. Further in vivo studies could be continued to assess the therapeutic efficiency of the prepared system.

Background The oral administration of the gum resin extracts of Indian frankincense (Boswellia serrata Roxb. ex Colebr) results in very low plasma concentrations of boswellic acids (BAs), being far below the pharmacologically active concentrations required in vitro for anti-inflammatory activity. For that reason the use of Indian frankincense in clinical practice and pharmaceutical development has substantially lagged behind. Recently the application of new formulation technologies resulted in a formulation of frankincense extract with lecithin, which revealed improved absorption and tissue penetration of BAs in a rodent study, leading for the first time to plasma concentrations of BAs in the range of their anti-inflammatory activity. Purpose In order to verify these encouraging results in humans, the absorption of a standardized Boswellia serrata extract (BE) and its lecithin formulation (CSP) was comparatively investigated in healthy volunteers. Study design According to a randomized cross-over design with two treatments, two sequences and two periods, 12 volunteers alternatively received the lecithin-formulated Boswellia extract (CSP) or the non-formulated Boswellia extract (BE) at a dosage of 2 × 250 mg capsules. Methods The plasma concentrations of the six major BAs (KBA, AKBA, βBA, αBA, AβBA, AαBA) were determined using LC/MS. Results With the exception of KBA, a significantly higher (both in terms of weight-to-weight and molar comparison) and quicker absorption of BAs from the lecithin formulation was observed, leading to Cmax in the range required for the interaction with their molecular targets. Conclusion These findings pave the way to further studies evaluating the clinical potential of BAs, and verify the beneficial effect of lecithin formulation to improve the absorption of poorly soluble phytochemicals.

Herbal antidiabetic preparations are often used as an add-on therapy in diabetes. Hence in the present investigation the effect of boswellic acids (BA) on the bioavailability and hypoglycemic action of metformin in normal as well as diabetic rats was studied. In normal and streptozotocin induced diabetic rats the combination of metformin with BA increased all the pharmacokinetic parameters such as Cmax, AUC0-n, AUCtotal, t½, MRT and decreased the clearance, Vd markedly as compared to control group. In intestinal and liver microsomes BA at 10μM has shown CYP3A4 inhibitory activity significantly (p