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In this study, a series of nine novel heterocyclic compounds were synthesized through a concise three-step reaction process. The synthesis involved Knoevenagel condensation at the 5th position of the 2,4-thiazolidinedione or rhodanine ring-system. Comprehensive physicochemical and spectral analyses, including FTIR, Mass, 1H NMR and 13C NMR, were performed to characterize the synthesized compounds. The synthesized derivatives were subjected to evaluation for their potential in various therapeutic domains. In-vivo anti-diabetic activity was assessed diabetes induced wistar rats, anti-inflammatory effects were gauged using the carrageenan and formalin induced rat paw edema model. Additionally, the in-vitro PPAR-γ modulatory activity, glucose uptake by using Saccharomyces cerevisiae and rat hemidiaphragm and cyclooxygenase inhibitory activity along with scavenge free radicals was tested by FRAP and DPPH method. According to the potential binding patterns of the most potent anti-diabetic compounds, namely 7a and 13a with the active sites of target PPAR-γ (PDB ID: 5U5L), was obtained through molecular docking using Schrodinger’s Glide model. Among the tested compounds, the compound 13a demonstrated significant antidiabetic activity with reduction in blood glucose levels (108.5 ± 2.171 mg/dL), comparable to the effect of pioglitazone (101.66 ± 0.95 mg/dL), similarly anti-inflammatory activity at fourth hour paw volume 93.6% and thickness at 3.99 ± 0.076 mm, respectively closer to that of standard drug diclofenac sodium (91.2% and 4.7 ± 0.057 mm) in carrageenan-induced paw edema in rat. The compound 13a displayed promising COX-2 inhibitory activity (IC50 = 7.82 μM) and DPPH antioxidant activity showcasing its multifaceted therapeutic potential. This study not only presents multi-targeting approach and highlights the significant potential compounds as a lead molecule for further therapeutic development.

Introduction: Medicinal plants have played an essential role in the treatment of human diseases and their associated secondary complications since early childhood in the medical systems of China, India, Korea, and Japan. Aromadendrin is a phytochemical member of the flavonoid class found in many medicinal plants such as Persica vulgaris, Chionanthus retusus, Populus davidiana, Olea europaea, Spatholobus suberectus, Akschindlium godefroyanum, Chionanthus retusu, Cudrania tricuspidata, Populus davidiana, Hemiptelea davidii and Gelditsia sinensis. The purpose of this article is to summarize scientific information on the medicinal efficacy, pharmacological activity, and analytical aspects of aromadendrin in medicine. Methods: This article discusses the biological significance and therapeutic effects of aromadendrin along with its analytical aspects to know the therapeutic potential of aromadendrin in medicine. All scientific information about aromadendrin was collected from Google, PubMed, Scopus, and Science Direct. Additionally, aromadendrin belongs to the flavonoid class, so to know its health benefits, the biological importance of flavonoids will also be discussed in this article. Additionally, the analytical aspects of aromadendrin are also discussed in this article. Results: This article discusses the biological significance and therapeutic efficacy of aromadendrin in the treatment of human diseases. This study reveals aromadendrin immunosuppressive, antiproliferative, anti-inflammatory, gastroprotective, antibacterial, trypanocidal, anticandida, antioxidant and cytotoxic potential in medicine. In addition, aromadendrin also has significant effects on cardiac hypertrophy, glucose absorption, non-small cell lung cancer, liver damage, acute pancreatitis, enzymes, and multidrug resistance. However, analytical parameters for aromadendrin separation, isolation, and identification are also discussed in this article. Discussion and conclusion: Present work described the different pharmacological activities of aromadendrin with their molecular mechanism. The present study provides new insights into the biological applications of aromadendrin and will help explore its therapeutic potential for many types of human diseases. This study will help understand the biological potential and benefits of aromadendrin in medicine.

Parthenolide (PTL) is a new compound extracted from traditional Chinese medicine. In recent years, it has been proven to play an undeniable role in tumors, autoimmune diseases, and inflammatory diseases. Similarly, an increasing number of experiments have also confirmed the biological mechanism of PTL in these diseases. In order to better understand the development trend and potential hot spots of PTL in cancer and other diseases, we conducted a detailed bibliometric analysis. The purpose of presenting this bibliometric analysis was to highlight and inform researchers of the important research directions, co-occurrence relationships and research status in this field. Publications related to PTL research from 2002 to 2022 were extracted on the web of science core collection (WoSCC) platform. CiteSpace, VOSviewers and R package “bibliometrix” were applied to build relevant network diagrams. The bibliometric analysis was presented in terms of performance analysis (including publication statistics, top publishing countries, top publishing institutions, publishing journals and co-cited journals, authors and co-cited authors, co-cited references statistics, citation bursts statistics, keyword statistics and trend topic statistics) and science mapping (including citations by country, citations by institution, citations by journal, citations by author, co-citation analysis, and keyword co-occurrence). The detailed discussion of the results explained the focus and latest trends from the bibliometric analysis. Finally, the current status and shortcomings of the research field on PTLwere clearly pointed out for reference by scholars.

Background: Glycyrrhiza glabra L. (G. glabra) commonly known as liquorice is one of the highly exploited and utilized medicinal plant of the world. Since ancient times liquorice is considered as an auspicious and valuable traditional medicine across the world for treatment of various ailments. Method: Several electronic online scientific databases such as Science Direct, PubMed, Scopus, Scifinder, Google Scholar, online books and reports were assessed for collecting information. All the collected information was classified into different sections to meet the objective of the paper. Results: The electronic database search yielded 3908 articles from different countries. Out of them one ninety-eight articles published between 1956 and 2021 were included, corresponding to all detailed review on G. glabra and research on anti-inflammatories, antivirals and immunomodulatory through pre-clinical and clinical models. From all selective area of studies on G. glabra and its bioactive components it was established (including molecular mechanisms) as a suitable remedy as per the current requirement of pandemic situation arise through respiratory tract infection. Conclusion: Different relevant studies have been thoroughly reviewed to gain an insight on utility of liquorice and its bioactive constituents for anti-inflammatories, antivirals and immunomodulatory effects with special emphasized for prevention and treatment of COVID-19 infection with possible mechanism of action at molecular level. Proposed directions for future research are also outlined to encourage researchers to find out various mechanistic targets and useful value added products of liquorice in future investigations.

Pacová (Renealmia petasites Gagnep.) is a Brazilian native plant, usually cultivated in south regions of the country. Pacová was previously reported concerning their possible health benefits, mostly from folk medicine. However, only few works relates the health benefits with the composition of the fruit parts. In this context, this work aimed to bring, for the first time in literature, the chemical characterization in respect to lipid and terpene composition of R. petasites oilseed, performed by three different extraction methods (supercritical fluid extraction (SFE) with CO2, Soxhlet with petroleum ether (SOX), and maceration with hexane (MAC)). SFE was most selective for MUFAs, PUFAs, sesqui- and diterpenes. The main terpene identified in all extracts was 2-carene. The extracts presented poor AChE inhibition, and SOX presented potential inhibitory effect against lipoxygenase activity. Overall, R. petasites oilseed is a natural source of terpenes and their potential health benefits are highly encouraged to be investigated.

In the present study, a series of 3-(5-cyclohexyl-1,3,4-oxadiazol-2-yl)-N-substituted aniline have been synthesized by multistep reaction scheme. Benzohydrazide was used as the starting material. The structures of all synthesized compounds are characterized and confirmed by FT-IR, 1H and C13 NMR and mass spectral studies with the intention of developing the novel biologically active compounds. All title synthetic compounds were screened for their antidiabetic, anti-inflammatory and anticancer activities.

The use of honey locust in food prompted us to study its flowers for functional food constituents. Bioassay-guided purification of hexane, ethyl acetate and methanolic extracts of its flowers afforded three new betulinic acid esters (1–3), one new linalool carboxylic acid ester (4), known terpenoids (5–7) and known polyphenols (8–11), as elucidated by spectroscopic methods. The extracts and terpenoids 1–7 were tested for antiinflammatory and antioxidant activities against cyclooxygenase enzymes (COX-1 and -2) and lipid peroxidation (LPO), respectively. Compounds 1–7 at 25 µg/mL showed antiinflammatory activity as indicated by COX-1 and -2 enzymes inhibition at a range of 40–50% and 33–37%, respectively. The antiinflammatory activity of extracts at 100 and compounds at 25 µg/mL was superior to aspirin and comparable to other over the counter non-steroidal antiinflammatory drugs (NSAIDs) naproxen and ibuprofen. Compounds 1–7 did not show LPO activity.

Lepisorus thunbergianus (Kaulf.) (LET) is an evergreen fern found on rocks and tree trunks that is distributed in East and Southeast Asia. Our previous study showed that the methanol extract from LET had significant anti-oxidant activity, but the active components of LET are still unclear. In the present study, isovitexin, orientin, isoorientin and chlorogenic acid were isolated from LET under the guidance of antioxidant activity. In addition, the structure of isovitexin, orientin, isoorientin and chlorogenic acid was characterized using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and nuclear magnetic resonance spectroscopy (NMR). Orientin and isoorientin presented similar activities toward the DPPH, with half maximal inhibitory concentrations (IC50) of 15–17 μmol, and inhibition of reactive oxygen species (ROS) production by 50% at 100 μmol. Chlorogenic acid significantly inhibited intracellular ROS and nitric oxide (NO) production and had a strong effect toward DPPH. Furthermore, chlorogenic acid demonstrated decreased iNOS, COX-2, IFN-β and TNF-α gene expression. These findings demonstrate the potential anti-inflammatory effects of chlorogenic acid. Isoorientin, at a concentration of 100 μmol, showed 50% inhibition of human liver cancer cells (Huh7 and HepG2). These results suggest that compounds isolated from LET have potential to prevent liver cancer cell lines.

In the present work, the anti-inflammatory effect of 30 compounds containing 3-fluorophenyl pyrimidinylimidazo[2,1-b]thiazole was investigated. All final target compounds showed significant Inhibitory effect on p38α. P38α is considered one of the key kinases in the inflammatory process due to its regulatory effect on pro-inflammatory mediators. The final target compounds divided into four group based on the type of terminal moiety (amide and sulfonamide) and the linker between pyrimidine ring and terminal moiety (ethyl and propyl). Most compounds with terminal sulfonamide moiety and propyl linker between the sulfonamide and pyrimidine ring were the most potent among all synthesized final target compounds with sub-micromolar IC 50s . Compound 24g (with p-Cl benzene sulfonamide and propyl linker) exhibited the highest activity over P38α with IC 50 0.68 µM. All final target compounds were tested for their ability to inhibit nitric oxide release and prostaglandin E2 production. Compounds having amide terminal moiety with ethyl linker showed higher inhibitory activity for nitric oxide release and compound 21d exhibited the highest activity for nitric oxide release with IC 50 1.21 µM. Compounds with terminal sulfonamide moiety and propyl linker showed the highest activity for inhibiting PGE2 production and compounds 24i and 24g had the lowest IC 50s with value 0.87 and 0.89 µM, respectively. Compounds 21d, 22d and 24g were tested for their ability to inhibit over expression of iNOS, COX1, and COX2. In addition the ability of compounds 21d, 22d and 24g to inhibit inflammatory cytokines were determined. Finally molecular docking of the three compounds were performed on P38α crystal structure to expect their mode of binding., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The arid plant Prosopis cineraria (Fabaceae) is known as Khejri in India or the golden tree of Indian deserts. The dried pods are consumed as a vegetable and leaves as traditional medicine to cure a wide range of diseases in the state of Rajasthan, India. The pods of this plant have not been investigated for their bioactive components, hence we have done so in this study. The dried pods were boiled with water to afford the aqueous extract. Extraction of the residue gave methanolic extract. The lipid peroxidation (LPO) and cyclooxygenase enzymes (COX-1 and -2) inhibitory activities of extracts and major compounds present in the bioactive extracts were then determined. Purification of bioactive extracts yielded compounds 1–7. The absorbance of 1–7 at 570 nm ranged between 0.15 and 0.45 at 50 μg/mL whereas vitamin C and tert-butylhydroquinone (TBHQ) at 25 μg/mL gave an absorbance of 0.5 in the MTT [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide] assay. At 25 μg/mL concentration, compounds 1–7 inhibited LPO, COX-1 and -2 enzymes between the ranges of 15–87%, 21–67% and 16–59%, respectively. This is the first report of the chemical and biological activities of the edible part of this plant.

Background: Mildronate is a useful anti-ischemic agent and has antiinflammatory, antioxidant, and neuroprotective activities. The aim of this study is to investigate the potential neuroprotective effects of mildronate in the experimental rabbit spinal cord ischemia/reperfusion injury (SCIRI) model., Methods: Rabbits were randomized into 5 groups of 8 animals as groups 1 (control), 2 (ischemia), 3 (vehicle), 4 (30 mg/kg methylprednisolone [MP]), and 5 (100 mg/kg mildronate). The control group underwent only laparotomy. The other groups have the spinal cord ischemia model by a 20-minute aortic occlusion just caudal to the renal artery. The malondialdehyde and catalase levels and caspase-3, myeloperoxidase, and xanthine oxidase activities were investigated. Neurologic, histopathologic, and ultrastructural evaluations were also performed., Results: The serum and tissue myeloperoxidase, malondialdehyde, and caspase-3 values of the ischemia and vehicle groups were statistically significantly higher than those of the MP and mildronate groups (P < 0.001). Serum and tissue catalase values of the ischemia and vehicle groups were statistically significantly lower than those of the control, MP, and mildronate groups (P < 0.001). The histopathologic evaluation showed a statistically significantly lower score in the mildronate and MP groups than in the ischemia and vehicle groups (P < 0.001). The modified Tarlov scores of the ischemia and vehicle groups were statistically significantly lower than those of the control, MP, and mildronate groups (P < 0.001)., Conclusions: This study presented the antiinflammatory, antioxidant, antiapoptotic, and neuroprotective effects of mildronate on SCIRI. Future studies will elucidate its possible use in clinical settings in SCIRI., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Apoprotein E (apoE) is synthesized by a number of tissues including the liver, brain, adipose tissue, and artery wall. The majority of apoE is found in the plasma associated with specific lipoprotein subclasses and is derived primarily from the liver. However the fact that apoE expression is sustained in nonhepatic tissues suggests that the local production must have some unique functional attribute. ApoE is involved in many steps in lipid and lipoprotein homeostasis, for the triglyceride-rich lipoproteins and for HDL. ApoE is also important for lipid homeostasis in the brain, artery wall, and adipose tissue through its synthesis by glial cells, adipocytes, and macrophages. In addition, nonlipid related functions have also been attributed to apoE, including effects on immune response and inflammation, oxidation, and smooth muscle proliferation and migration. Some of these effects have been shown to be dependent upon different domains of the protein, different concentrations, and lipidation state. Thus, this multifunctional protein impacts normal and pathophysiology at multiple levels.

Background: It is known that hydrogels based on carboxymethyl chitosan (CMCS) have properties controling microbial growth, reducing inflammatory cell infiltration, and promoting collagen deposition. Plantamajoside (PMS), a natural Chinese herbal medicine with biological activity, has the properties of reducing inflammation, anti-oxidation, and promoting wound healing. However, the effects of carboxymethyl chitosan/plantamajoside hydrogel on partial thickness burn wounds remain unclear., Methods: The healing effect of carboxymethyl chitosan/plantamajoside hydrogel was evaluated by in vitro cell viability assay, cell migration assay, and further evaluated in a rat model of partial-thickness burn wounds., Results: The hydrogels were highly porous with a pore size of about 250 μm, and these pores were interconnected. After adding plantamajoside, a dense microstructure was further formed. The hydrogels containing 0.25% plantamajoside significantly increased the viability and migration of L929 cells (P < 0.05). Carboxymethyl chitosan/plantamajoside hydrogel significantly improved wound healing, granulation tissue proliferation and re-epithelialization, and promoted collagen deposition (P < 0.05). Carboxymethyl chitosan/plantamajoside hydrogel also significantly decreased IL (interleukin)-1β, IL-6 and TNF-α expression, and increased IL-10 expression (P < 0.05). Furthermore, carboxymethyl chitosan/plantamajoside hydrogel significantly promoted the expression levels of VEGF, CD31, α-SMA (α-smooth muscle actin) and collagen III, and reduced the expression level of collagen Ⅰ (P < 0.05). Our data suggest that carboxymethyl chitosan/plantamajoside hydrogel promotes burn wound healing by accelerating angiogenesis and collagen deposition and reducing the inflammatory response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: Lamotrigine, an anticonvulsant drug with inhibition properties of multi-ion channels, has been shown to be able to attenuates secondary neuronal damage by influencing different pathways. The aim of this study was to look into whether lamotrigine treatment could protect the spinal cord from experimental spinal cord ischemia-reperfusion injury., Materials and Methods: Thirty-two rats, eight rats per group, were randomly assigned to the sham group in which only laparotomy was performed, and to the ischemia, methylprednisolone and lamotrigine groups, where the infrarenal aorta was clamped for thirty minutes to induce spinal cord ischemia-reperfusion injury. Tissue samples belonging to spinal cords were harvested from sacrificed animals twenty-four hours after reperfusion. Tumor necrosis factor-alpha levels, interleukin-1 beta levels, nitric oxide levels, superoxide dismutase activity, catalase activity, glutathione peroxidase activity, malondialdehyde levels and caspase-3 activity were studied. Light and electron microscopic evaluations were also performed to reveal the pathological alterations. Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test was used to evaluate neurofunctional status at the beginning of the study and just before the animals were sacrificed., Results: Lamotrigine treatment provided significant improvement in the neurofunctional status by preventing the increase in cytokine expression, increased lipid peroxidation and oxidative stress, depletion of antioxidant enzymes activity and increased apoptosis, all of which contributing to spinal cord damage through different paths after ischemia reperfusion injury. Furthermore, lamotrigine treatment has shown improved results concerning the histopathological and ultrastructural scores and the functional tests., Conclusion: These results proposed that lamotrigine may be a useful therapeutic agent to prevent the neuronal damage developing after spinal cord ischemia-reperfusion injury., Competing Interests: Declarations of competing interest None., (Copyright © 2021. Published by Elsevier Ltd.)

Nitrogen heterocyclic rings have participated to constitute most of the drugs and several pharmacologically related compounds. The existence of such hetero atoms/groups in heterocyclic systems privileged specificities in their biological objectives. Particularly, quinazoline and triazole are biologically imperative platforms known to be linked with various pharmacological activities. Some of the prominent pharmacological responses ascribed to these systems are analgesic, antiinflammatory, anticonvulsant, hypnotic, antihistaminic, antihypertensive, anticancer, antimicrobial, antitubercular, antiviral and antimalarial activities. This diversity in the pharmacological outputs for both triazole and quinazoline systems has encouraged the medicinal chemistry researchers to create several chemical routes aiming at the incorporation of two rings in one molecule named triazoloquinazoline system. This system has shown multiple potential activities against numerous targets. Correlation the specific structural features of triazoloquinazoline system with its pharmacological purposes has successively been achieved by performing several pharmacological examinations and structure-activity relationship studies. The development of triazoloquinazoline derivatives and the understanding of their pharmacological targets offer opportunities for novel therapeutics. This review mainly emphases on the medicinal chemistry aspects of triazoloquinazolines including synthesis, reactivity, biological activity and structure activity relationship studies (SARs). Moreover, this review collates literature reported by researchers on triazoquinazolines and provides detailed attention on their analogs pharmacological activities in the perspective of drug development and discovery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to investigate the possible neuroprotective effects of cinnamaldehyde (CA) on secondary brain injury after traumatic brain injury (TBI) in a rat model., Methods: Rats were randomly divided into 4 groups: control (n = 9), TBI (n = 9), vehicle (0.1% Tween 80; n = 8), and CA (100 mg/kg) (n = 9). TBI was induced by the weight-drop model. In brain tissues, myeloperoxidase activity and the levels of luminol-enhanced and lucigenin-enhanced chemiluminescence were measured. Interleukin 1β, interleukin 6, tumor necrosis factor α, tumor growth factor β, caspase-3, and cleaved caspase-3 were evaluated with an enzyme-linked immunosorbent assay method. Brain injury was histopathologically graded after hematoxylin-eosin staining. Y-maze and novel object recognition tests were performed before TBI and within 24 hours of TBI., Results: Higher myeloperoxidase activity levels in the TBI group (P < 0.001) were suppressed in the CA group (P < 0.05). Luminol-enhanced and lucigenin-enhanced chemiluminescence, which were increased in the TBI group (P < 0.001, for both), were decreased in the group that received CA treatment (P < 0.001 for both). Compared with the increased histologic damage scores in the cerebral cortex and dentate gyrus of the TBI group (P < 0.001), scores of the CA group were lower (P < 0.001). Decreased number of entries and spontaneous alternation percentage in the Y-maze test of the TBI group (P < 0.05 and P < 0.01, respectively) were not evident in the CA group., Conclusions: CA has shown neuroprotective effects by limiting neutrophil recruitment, suppressing reactive oxygen species and reducing histologic damage and acute hippocampal dysfunction., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: The fact that physical activity besides central cholinergic enhancement contributes in improving neuronal function and spastic plasticity, recommends the use of the anticholinesterase and cholinergic drug galantamine with/without exercise in the management of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS)., Materials and Methods: Sedentary and 14 days exercised male Sprague Dawley rats were subjected to EAE. Hereafter, exercised rats continued on rotarod for 30 min for 17 consecutive days. At the onset of symptoms (day 13), EAE sedentary/exercised groups were subdivided into untreated and post-treated with galantamine. The disease progression was assessed by EAE score, motor performance, and biochemically using cerebrospinal fluid (CSF). Cerebellum and brain stem samples were used for histopathology and immunohistochemistry analysis., Key Findings: Galantamine decreased EAE score of sedentary/exercised rats and enhanced their motor performance. Galantamine with/without exercise inhibited CSF levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6), and Bcl-2-associated X protein (Bax), besides caspase-3 and forkhead box P3 (Foxp3) expression in the brain stem. Contrariwise, it has elevated CSF levels of brain derived neurotrophic factor (BDNF) and B-cell lymphoma (Bcl-2) and enhanced remyelination of cerebral neurons. Noteworthy, exercise boosted the drug effect on Bcl-2 and Bax., Significance: The neuroprotective effect of galantamine against EAE was associated with anti-inflammatory and anti-apoptotic potentials, along with increasing BDNF and remyelination. It also normalized regulatory T-cells levels in the brain stem. The impact of the add-on of exercise was markedly manifested in reducing neuronal apoptosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Physically active individuals are less likely to develop chronic pain, and physical exercise is an established strategy to control inflammatory diseases. Here, we hypothesized that 1) peripheral pro-inflammatory macrophages phenotype contribute to predisposition of the musculoskeletal to chronic pain, and that 2) activation of PPARγ receptors, modulation of macrophage phenotypes and cytokines through physical exercise would prevent persistent muscle pain. We tested these hypotheses using swimming exercise, pharmacological and immunochemical techniques in a rodent model of persistent muscle hyperalgesia. Swimming prevented the persistent mechanical muscle hyperalgesia most likely through activation of PPARγ receptors, as well as activation of PPARγ receptors by 15d-PGJ 2 and depletion of muscle macrophages in sedentary animals. Acute and persistent muscle hyperalgesia were characterized by an increase in pro-inflammatory macrophages phenotype, and swimming and the 15d-PGJ 2 prevented this increase and increased anti-inflammatory macrophages phenotype. Finally, IL-1β concentration in muscle increased in the acute phase, which was also prevented by PPARγ receptors activation through swimming. Besides, swimming increased muscle concentration of IL-10 in both acute and chronic phases, but only in the persistent phase through PPARγ receptors. Our findings suggest physical exercise activates PPARγ receptors and increases anti-inflammatory responses in the muscle tissue by modulating macrophages phenotypes and cytokines, thereby preventing the establishment of persistent muscle hyperalgesia. These results further highlight the potential of physical exercise to prevent chronic muscle pain., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Twelve undescribed lanostane-type triterpenes, and twenty-two known triterpenes were isolated and identified from a medicinal bracket fungus Fomitopsis pinicola (Sw.) P. Karst. The structures of these compounds were determined by spectroscopic and spectrometric analyses. The antiinflammatory potential of thirty-two triterpene compounds was evaluated using neutrophils as an assay model, and pinicolasin J was the most potent inhibitor of superoxide anion generation and elastase release, with IC 50 values of 1.81 ± 0.44 and 2.50 ± 0.64 μM, respectively. This study provides scientific insight into the nutritional supplement value and medicinal development of Fomitopsis pinicola., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system., Objective: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes., Study Design: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned expectant management. In addition to standard therapy, patients were randomized to receive either recombinant human antithrombin 250 mg loading dose followed by a continuous infusion of 2000 mg per 24 hours or an identical saline infusion until delivery. The primary outcome was days gained from randomization until delivery. The secondary outcome was composite neonatal morbidity score. A total of 120 women were randomized., Results: There was no difference in median gestational age at enrollment (27.3 weeks' gestation for the recombinant human antithrombin group [range, 23.1-30.0] and 27.6 weeks' gestation for the placebo group [range, 23.0-30.0]; P=.67). There were no differences in median increase in days gained (5.0 in the recombinant human antithrombin group [range, 0-75] and 6.0 for the placebo group [range, 0-85]; P=.95). There were no differences between groups in composite neonatal morbidity scores or in maternal complications. No safety issues related to recombinant human antithrombin were noted in this study, despite the achievement of supraphysiological antithrombin concentrations., Conclusion: The administration of recombinant human antithrombin in preterm preeclampsia neither prolonged pregnancy nor improved neonatal or maternal outcomes., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Although human adenovirus (ADV) infections are mild and self-limited in immunocompetent individuals, they can be severe and life-threatening in immunocompromised patients. Despite their significant clinical impact, there are not currently approved antiviral therapies for ADV infections. On the other hand, in some cases, the immune response induced by ADV infection can cause tissue damage. Even more, in the case of adenovirus vectors used in gene therapy, host immunity generally antagonize viral efficacy. Therefore, the need for searching an effective and safe therapy is increasing. In this work, we describe the antiadenoviral activity of the synthetic stigmastane (22S, 23S)-22,23-dihydroxystigmast-4-en-3-one (Compound 1) with already reported antiviral and antiinflammatory activities against other viruses of clinical importance. Compound 1 displayed no virucidal activity and did not affect ADV entry to the cells. The compound inhibited viral replication and it also reduced cytokine secretion in epithelial and inflammatory infected cells. Thus, Compound 1 would be a promissory drug potentially useful against adenoviral infections as well as an adjuvant of adenoviral vectors in gene therapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Prostate cancer is one of the most common cancers in men. Diosgenin and related compounds are potential cytotoxic agents. Twelve diverse analogues of long chain fatty acid/ester of diosgenin-7-ketoxime have been prepared. Six of the analogues exhibited significant anticancer activity against a panel of human cancer cell lines with IC 50 ranging from 12 to 35μM. Compound 16, the best representative of the series exerted S phase arrest in DU145 prostate cancer cells and induced apoptosis through caspase pathway. Additionally, these analogues inhibited lipopolysaccharide induced pro-inflammatory cytokines (TNF-α and IL-6) up to 47.7% and 23.3% respectively. Compound 16 was found to be safe in acute oral toxicity in Swiss albino mice up to 300mg/kg dose. The anticancer and antiinflammatory properties of compound 16 are important and can further be optimized for a better anti-prostate cancer candidate., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Utilizing the biological activities of compounds by encapsulating natural components in stable nanoparticles is an important strategy for a variety of biomedical and healthcare applications. In this study, quercetin-loaded silica nanoparticles were synthesized using an oil-in-water microemulsion method, which is a suitable system for producing functional nanoparticles of controlled size and shape. The resulting quercetin-loaded silica nanoparticles were spherical, highly monodispersed, and stable in an aqueous system. Superoxide radical scavenging effects were found for the quercetin-loaded silica nanoparticles as well as free quercetin. The quercetin-loaded silica nanoparticles showed cell viability comparable to that of the controls. The amounts of proinflammatory cytokines produced by macrophages, such as interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha, were reduced significantly for the quercetin-loaded silica nanoparticles. These results suggest that the antioxidative and antiinflammatory activities of quercetin are maintained after encapsulation in silica. Silica nanoparticles can be used for the effective and stable incorporation of biologically active natural components into composite biomaterials., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Hashimoto's encephalopathy (HE) is a rare syndrome of progressive or relapsing-remitting encephalopathy associated with elevated serum anti-thyroid antibody concentrations. It is thought to be an autoimmune process that generally responds well to high-dose corticosteroids and other immunomodulatory therapies. However, some patients are unresponsive to steroids or are unable to receive immune therapy. A viable alternative is needed for this group. Given that seizure and EEG abnormalities are commonly associated with this syndrome, we postulate that treatment with levetiracetam, which has duel anti-inflammatory and anti-seizure mechanisms, might show clinical benefit. We present the cases of two patients who met the criteria for HE but were unable to receive steroids due to labile diabetes. They were both successfully treated with levetiracetam., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Our group previously showed that colchicine treatment is associated with decreased early recurrence rate after ablation for atrial fibrillation (AF)., Objective: The purpose of this study was to test the mid-term efficacy of colchicine in reducing AF recurrences after a single procedure of pulmonary vein isolation in patients with paroxysmal AF. Assessment of quality-of-life (QOL) changes was a secondary objective., Methods: Patients with paroxysmal AF who were scheduled for ablation were randomized to a 3-month course of colchicine 0.5 mg twice daily or placebo and were followed for a median of 15 months (with a 3-month blanking period). QOL was assessed with a general-purpose health-related QOL tool (26-item World Health Organization QOL questionnaire) at baseline and after 3 and 12 months., Results: Two hundred twenty-three randomized patients underwent ablation, and 206 patients were available for analysis (144 male, age 62.2 ± 5.8 years). AF recurrence rate in the colchicine group was 31.1% (32/103) vs 49.5% (51/103) in the control group (P = .010), translated in a relative risk reduction of 37% (odds ratio 0.46, 95% confidence interval 0.26-0.81). The number needed to treat was 6 (95% confidence interval 3.2-19.8). Physical domain QOL scores at 12 months were 63.6 ± 13.8 in the colchicine group and 52.5 ± 18.1 in controls, whereas psychological domain scores were 56.1 ± 13.7 vs 44.7 ± 17.3, respectively (P <.001, for both)., Conclusion: Colchicine treatment after pulmonary vein isolation for paroxysmal AF is associated with lower AF recurrence rates after a single procedure. This reduction is accompanied by corresponding improvements in physical and psychological health-related QOL scores., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)