Synthesis, biological evaluation and computational studies of acrylohydrazide derivatives as potential Staphylococcus aureus NorA efflux pump inhibitors.

The NorA efflux pump decreases the intracellular concentration of fluoroquinolones (ciprofloxacin, norfloxacin) by effluxing them from Staphylococcus aureus cells. The synthesis of novel acrylohydrazide derivatives was achieved using well-known reactions and were characterized by various spectroscopy techniques. The synthesized 50 compounds were evaluated for the NorA efflux pump inhibition activity against S. aureus SA-1199B (norA++) and K1758 (norA-) strains. The study provided two most active compounds viz. 19 and 52. Compound 19 was found to be most active in potentiating effect of norfloxacin and also it showed enhanced uptake, efflux inhibition in ethidium bromide assay. Further compound 19 also enhanced post antibiotic effect and reduced mutation prevention concentration of norfloxacin. The homology modeling study was performed to elucidate three-dimensional structure of NorA. Docking studies of potent molecules were done to find the binding affinity and interaction with active site residues. Further, all the tested compounds exhibited good ADME and drug-likeness properties in- silico. Based on the in-silico studies and detailed in vitro studies, acrylohydrazides derivatives may be considered as potential NorA EPI candidates.

MsrA Efflux Pump Inhibitory Activity of Piper cubeba L.f. and its Phytoconstituents against Staphylococcus aureus RN4220.

MsrA, an efflux pump belonging to ATP-binding cassette (ABC) transporter family that conferred resistance to macrolides, was detected in Staphylococcus aureus strains. Herein, we report the isolation of phytoconstituents from Piper cubeba fruit methanol extract and investigated their efflux pump inhibitory potential against S. aureus MsrA pump. Four isolated compounds, viz. pellitorine, sesamin, piperic acid and tetrahydropiperine studied in combination with erythromycin in S. aureus RN4220, exhibited 2-8-fold reduction in minimum inhibitory concentration (MIC) of erythromycin. Pellitorine and sesamin decreased MIC of erythromycin by 8-fold. The real-time fluorometry-based efflux and accumulation studies of ethidium bromide (EtBr) on S. aureus RN4220 in the presence of these compounds showed reduced efflux and enhanced uptake, thus indicating inhibition of the efflux pump. Pellitorine showed significant post-antibiotic effect of erythromycin. The results revealed that the primary mechanism of action of these compounds involves steady ATP production impairment.

Pyrazole-coumarin and pyrazole-quinoline chalcones as potential antitubercular agents.

Pyrazole, coumarin, and quinoline are medicinally important moieties. In this study, two series of novel pyrazole-coumarin chalcones and pyrazole-quinoline chalcones were synthesized using multiple-step reactions. All the synthesized compounds were well characterized using different spectroscopic techniques including 1 H and 13 C nuclear magnetic resonance, high-resolution mass spectroscopy, and electrospray ionization-mass spectrometry. The compounds were evaluated for their antitubercular activity against the Mycobacterium tuberculosis H37Rv strain using the microplate Alamar Blue assay, and the minimal inhibitory concentrations (MIC) of the compounds were determined. Among the 32 tested compounds, compounds 3e, 3u, and 7h showed an MIC value of 3.125 µg/ml, and they were found to be nontoxic. Molecular docking studies of the compounds with the enzyme DprE1 revealed the probable mechanism of action. The chalcone derivatives exhibited binding affinity values between -7.047 and -9.353 kcal/mol. ADME parameters were predicted using the QikProp module of the Schrödinger software, and these compounds exhibited good pharmacological and oral absorption properties.

2'-Hydroxy flavanone derivatives as an inhibitors of pro-inflammatory mediators: Experimental and molecular docking studies.

2'-Hydroxy flavanone (1) was previously isolated from Mimosa pudica (L.) whole plant and was found to exhibit anti-inflammatory effects in vitro. There are also reports on anti-inflammatory properties of compounds bearing flavanone/chromone nucleus. Taking this into account, fourteen derivatives of 2'-hydroxy flavanone (1) were synthesized and evaluated against pro-inflammatory mediators (TNF-α, IL-1ß and NO) in in vitro and in vivo models. Results directed that among the synthesized compounds, four derivatives (11-14) showed profound inhibition of pro-inflammatory mediators as compared to the lead molecule. Further, 11-14 demonstrated comparable anti-inflammatory activity with ibuprofen in carrageenan-induced rat paw edema assay and appreciable inhibition of lipopolysaccharide (LPS) induced pro-inflammatory mediators (TNF-α and IL-1ß) in Sprague Dawley (SD) rats. The synthesized compounds were further subjected to molecular docking analysis and in silico prediction of pharmacokinetic properties.

Synthesis, biological evaluation and docking analysis of 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones as potential cyclooxygenase-2 (COX-2) inhibitors.

As a part of our continued efforts to discover new COX inhibitors, a series of 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones were synthesized and evaluated for in vitro COX inhibitory potential. Within this series, seven compounds (3a-d, 3h, 3k and 3q) were identified as potential and selective COX-2 inhibitors (COX-2 IC50's in 1.79-4.35µM range; COX-2 selectivity index (SI)=6.8-16.7 range). Compound 3b emerged as most potent (COX-2 IC50=1.79µM; COX-1 IC50 >30µM) and selective COX-2 inhibitor (SI >16.7). Further, compound 3b displayed superior anti-inflammatory activity (59.86% inhibition of edema at 5h) in comparison to celecoxib (51.44% inhibition of edema at 5h) in carrageenan-induced rat paw edema assay. Structure-activity relationship studies suggested that N-phenyl ring substituted with p-CF3 substituent (3b, 3k and 3q) leads to more selective inhibition of COX-2. To corroborate obtained experimental biological data, molecular docking study was carried out which revealed that compound 3b showed stronger binding interaction with COX-2 as compared to COX-1.

Wound-healing effect of topical nanoemulsion-loaded cream and gel formulations of Hippophae rhamnoides L. (sea buckthorn) fruit oil and their acute dermal toxicity study on female SD rats.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of topical nanoemulsion (NE)-loaded cream and gel formulations of Hippophae rhamnoides L. (sea buckthorn [SBT]) fruit oil for wound healing. MATERIALS AND METHODS: The NE-loaded cream and gel formulations of H. rhamnoides L. (SBT) fruit oil (IPHRFH) were prepared and evaluated for their wound-healing activity on female Sprague-Dawley (SD) rats. They were further divided into groups (seven) and the wound-healing activity was determined by measuring the area of the wound on the wounding day and on the 0th, 4th, 8th, and 10th days. The acute dermal toxicity of the formulations was assessed by observing the erythema, edema, and body weight (BW) of the rats. RESULTS: The topical NE cream and gel formulations of H. rhamnoides L. (SBT) fruit oil showed significant wound-healing activity in female SD rats. The cream formulation of IPHRFH showed 78.96%, the gel showed 72.59% wound contraction on the 8th day, whereas the positive control soframycin (1% w/w framycetin) had 62.29% wound contraction on the 8th day. The formulations also showed a good acute dermal toxicity profile with no changes significantly affecting BW and dermal alterations. CONCLUSIONS: The results of this study indicate that topical NE-loaded cream and gel formulation of H. rhamnoides L. (SBT) fruit oil are safe and effective for wound healing. The formulations showed no signs of acute dermal toxicity in female SD rats.

Synthesis of novel celecoxib analogues by bioisosteric replacement of sulfonamide as potent anti-inflammatory agents and cyclooxygenase inhibitors.

Two series of celecoxib analogues having 1,5-diaryl relationship were synthesized. The key strategy of the molecular design was oriented towards exploring bioisosteric modifications of the sulfonamide moiety of celecoxib. First series (2a-2i) of celecoxib analogues bearing cyano functionality in place of sulfonamide moiety was synthesized by the reaction of appropriate trifluoromethyl-ß-diketones (5a-5i) with 4-hydrazinylbenzonitrile hydrochloride (4) in ethanol. Cyano moiety of pyrazoles 2 was then converted into corresponding carbothioamides 3 by bubbling H2S gas in the presence of triethylamine. All the synthesized compounds (2a-2i and 3a-3i) were screened for their in vivo anti-inflammatory (AI) activity using carrageenan-induced rat paw edema assay. COX-1 and COX-2 inhibitory potency was evaluated through in vitro cyclooxygenase (COX) assays. Compounds 2a, 2b, 2c, 2e and 3c showed promising AI activity at 3-4h after the carrageenan injection that was comparable to that of the standard drug indomethacin. Although compounds 3d, 3e and 3f exhibited more pronounced COX-2 inhibition but they also inhibit COX-1 effectively thus being less selective against COX-2. Three compounds 2a, 2f and 3a were found to have a COX profile comparable to the reference drug indomethacin. However 2e, 3b, 3c and 3i compounds were the most potent selective COX-2 inhibitors of this study with 3b showing the best COX-2 profile. In order to better rationalize the action and the binding mode of these compounds, docking studies were carried out. These studies were in agreement with the biological data.

Rotenoids from Boerhaavia diffusa as potential anti-inflammatory agents.

Five new (2, 3, 5, 7, and 9) and four known rotenoids (1, 4, 6, and 8) were isolated from a methanol extract of Boerhaavia diffusa roots. The structures of the new rotenoids were elucidated by spectroscopic data interpretation. The 70% ethanol extract, a rotenoid-rich fraction, and all isolated rotenoids were evaluated for their COX-1 and COX-2 inhibitory activities. Among the rotenoids tested, compound 7 showed the most potent COX-1 and COX-2 inhibition, with IC50 values of 21.7 ± 0.5 and 25.5 ± 0.6 µM, respectively. Boeravinone B (6) exhibited significant anti-inflammatory activity (56.6% at 50 mg/kg) when evaluated in an in vivo carrageenan-induced rat paw model.

Evaluation of the in vitro and in vivo anti-inflammatory activity of Gymnosporia montana (Roth). Benth leaves.

ETHNO-PHARMACOLOGICAL RELEVANCE: Gymnosporia montana (Roth) Benth an herbaceous shrub used in Indian traditional medicine their leaves decoction was used as mouthwash to get relieve from toothache, hence it is also known as Dantakashta in Sanskrit language which means the plant used for tooth problems. Traditionally the leaves juice used to alleviate inflammation and in some parts of India like Saurashtra in Gujarat, leaves were chewed as a folklore cure for Jaundice and in Bhandra region Karnataka, leaves extract mixed with cow milk used for jaundice. Hepatoprotective activity for G. montana leaves was well reported however, its use for inflammation and toothache are still not studied to investigate active phytoconstituents responsible for anti-inflammatory activity. AIM OF THE STUDY: The present study aimed at bioactivity guided isolation of G. montana leaves extracts using inhibition of pro-inflammatory mediators such as nitric oxide (NO), tumor necrosis factor (TNF-α), and interleukins (IL-1ß and IL-6) in RAW 264.7 cells in vitro assay to yield bioactive phytoconstituents. MATERIALS AND METHODS: The n-hexane, ethyl acetate and methanol extracts prepared from G. montana leaves were evaluated for cell viability using MTT assay. The effect of extracts to inhibit the pro-inflammatory mediators like NO, TNF-α, IL-1ß and IL-6 in RAW 264.7 macrophages was measured by enzyme-linked immunosorbent assay (ELISA). The quantitative analysis of the isolated phytoconstituents was performed using quantitative Nuclear Magnetic Resonance (qNMR). RESULTS: The n-hexane, ethyl acetate, and methanol extracts of G. montana leaves exhibited cell viability in the range of 97.43-84.88% at 50 µg/mL concentration in RAW 264.7 macrophages. In-vitro evaluation of extracts showed that n-hexane extract was most effective in inhibiting NO, TNF-α, IL-1ß and IL-6 inflammatory mediators at 50 µg/mL in lipopolysaccharides (LPS) stimulated RAW 264.7 cells. Further n-hexane extract, its fraction GMHA3 and ß-amyrin exhibited significant anti-inflammatory activity at 100, 50 and 30 mg/kg per oral, respectively in carrageenan-induced rat paw edema. The quantitative analysis by qNMR revealed ß-amyrin as a major compound in the n-hexane extract. CONCLUSIONS: In vitro and in vivo bioassay results suggested that G. montana n-hexane extract, its fraction GMHA3 and ß-amyrin exhibits significant anti-inflammatory activity proves the traditional uses of G. montana leaves. The reported activity of ß-amyrin for periodontitis provides evidence of profound the use of G. montana leaves for toothache and anti-inflammatory activity.

Quantitative analysis of tiliroside and other flavonoid glycosides in Hippophae salicifolia D. Don leaves by HPLC-PDA.

A new HPLC-PDA method was developed and validated for simultaneous determination of five phenolic compounds (trans-and cis- isomers of tiliroside, quercetin-3-O-ß-D-glucoside, ellagic acid, kaempferol-3-O-ß-D-glucoside and isorhamnetin-3-O-glucoside) in the leaves of Hippophae salicifolia D. Don. Of the five compounds, three (tiliroside, quercetin-3-O-ß-D-glucoside and ellagic acid) were isolated and characterised by spectroscopy techniques. The developed HPLC method provided a selective, sensitive and rapid analysis with good linearity (r2> 0.999), accuracy and precision. Also, the leaves of H. salicifolia were extracted by three different extraction techniques viz. reflux, microwave and ultrasound. Methanolic extracts prepared by reflux method showed the highest content of all the five compounds.

Synthesis, biological evaluation and molecular docking studies of stellatin derivatives as cyclooxygenase (COX-1, COX-2) inhibitors and anti-inflammatory agents.

Stellatin (4), isolated from Dysophylla stellata is a cyclooxygenase (COX) inhibitor. The present study reports the synthesis and biological evaluation of new stellatin derivatives for COX-1, COX-2 inhibitory and anti-inflammatory activities. Eight derivatives showed more pronounced COX-2 inhibition than stellatin and, 17 and 21 exhibited the highest COX-2 inhibition. They also exhibited the significant anti-inflammatory activity in TPA-induced mouse ear edema assay and their anti-inflammatory effects were more than that of stellatin and indomethacin at 0.5mg/ear. The derivatives were further evaluated for antioxidant activity wherein 16 and 17 showed potent free radical scavenging activity against DPPH and ABTS radicals. Molecular docking study revealed the binding orientations of stellatin and its derivatives into the active sites of COX-1 and COX-2 and thereby helps to design the potent inhibitors.

Simultaneous determination of naphthalene and anthraquinone derivatives in Rumex nepalensis Spreng. roots by HPLC: comparison of different extraction methods and validation.

INTRODUCTION: Rumex nepalensis contains mainly anthraquinone and naphthalene derivatives. Although HPLC methods have been reported for the analysis of anthraquinones, neither a phytochemical analysis of Rumex species nor the simultaneous determination of anthraquinone and naphthalene derivatives in other samples has been reported so far. OBJECTIVE: To develop and validate a HPLC method for the simultaneous determination of anthraquinone and naphthalene derivatives in R. nepalensis roots. METHODOLOGY: Anthraquinones and naphthalenes were extracted from R. nepalensis roots by three methods (reflux, ultrasonication and pressurized liquid extraction) using methanol. Separation was achieved on an RP C18 column with a gradient mobile phase consisting of 0.05% orthophosphoric acid in water (solvent A) and methanol (solvent B) using a UV detector (254 nm). RESULTS: Small differences were observed in the contents of anthraquinone and naphthalene derivatives extracted by the three methods. Chrysophanol-8-O-ß-D-glucopyranoside and nepodin were detected as major constituents. The method showed a good linearity (r² > 0.9992), high precision (RSD < 5%) and a good recovery (97-105%) of the compounds. The lowest detection limit was found to be 0.97 ng and the method was found to be robust. CONCLUSION: Reflux and ultrasonication were found to be the best suited methods for the extraction of glycosides and aglycones, respectively. The developed and validated HPLC method is simple, precise and accurate; and can hence be recommended as the method of choice for the analysis of anthraquinones and naphthalenes in R. nepalensis and other Rumex species for both quality control as well as routine analytical purposes.

Natural Product Inhibitors of Cyclooxygenase (COX) Enzyme: A Review on Current Status and Future Perspectives.

BACKGROUND: Several clinically used COX-1 and COX-2 inhibitor drugs were reported to possess severe side effects like GI ulcers and cardiovascular disturbances, respectively. Natural products being structurally diverse always attracted the attention of chemists/ medicinal chemists as a potential source of lead molecules in the drug discovery process. COX-2 inhibitory natural products also possess potential cancer chemopreventive property against various cancers including that of colon, breast and prostate. METHODS: Various in vitro, in vivo and in silico standardized methods were used to evaluate COX inhibition property of different secondary metabolites isolated from plant, microbial and marine origin. RESULTS: We had earlier reported a detailed account of natural product inhibitors of COX reported during 1995-2005, in 2006. In the proposed review, we report 158 natural product inhibitors of COX during 2006 to 2019 belonging to various secondary metabolite classes such as alkaloids, terpenoids, polyphenols as flavonoids, chromones, coumarins, lignans, anthraquinones, naphthalenes, curcuminoids, diarylheptanoids and miscellaneous compounds of plant and marine origin. Further Structure Activity Relationship (SAR) studies of possible leads are also included in the article. CONCLUSION: COX inhibitors served as a potential source of lead molecules for the discovery and development of anti-inflammatory drugs. Compilation of natural product and semisynthetic inhibitors of COX may serve as valuable information to the researchers who are looking for possible lead molecules from a natural source to conduct further preclinical and clinical studies.

Natural Anti-inflammatory Compounds as Drug Candidates in Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, and oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. Therefore, to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals, including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol, were reported molecules for the treatment of AD. Several alkaloids, such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine and anatabine, have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.

Origanum vulgare L.: In vitro Assessment of Cytotoxicity, Molecular Docking Studies, Antioxidant and Anti-inflammatory Activity in LPS Stimulated RAW 264.7 Cells.

BACKGROUND: Inflammation involves a dynamic network that is highly regulated by signals that initiate the inflammation process as well as signals that downregulate it. However, an imbalance between the two leads to tissue damage. Throughout the world, inflammatory disease becomes common in the aging society. The drugs which are used clinically have serious side effects. Natural products or compounds derived from natural products show diversity in structure and play an important role in drug discovery and development. OBJECTIVE: Oreganum Vulgare is used in traditional medicine for various ailments including respiratory and rheumatic disorders, severe cold, suppression of tumors. The current study aims to evaluate the anti-inflammatory potential by evaluating various in vitro parameters. METHODS: Inflammation-induced in macrophages via LPS is the most accepted model for evaluating the antiinflammatory activity of various plant extracts and lead compounds. RESULTS: The extracts (OVEE, OVEAF) as well as the isolated compound(OVRA)of Oreganum Vulgare inhibit the pro-inflammatory cytokines (IL-6 and TNF-α) and NO without affecting cell viability. CONCLUSION: Our study established that the leaf extracts of Oreganum vulgare L. exhibit anti-inflammatory activity and thus confirm its importance in traditional medicine.

Design, Synthesis, Molecular Modelling, and Biological Evaluation of Oleanolic Acid-Arylidene Derivatives as Potential Anti-Inflammatory Agents.

INTRODUCTION: Oleanolic acid, a pentacyclic triterpenic acid, is widely distributed in medicinal plants and is the most commonly studied triterpene for various biological activities, including anti-allergic, anti-cancer, and anti-inflammatory. METHODS: The present study was carried out to synthesize arylidene derivatives of oleanolic acid at the C-2 position by Claisen Schmidt condensation to develop more effective anti-inflammatory agents. The derivatives were screened for anti-inflammatory activity by scrutinizing NO production inhibition in RAW 264.7 cells induced by LPS and their cytotoxicity. The potential candidates were further screened for inhibition of LPS-induced interleukin (IL-6) and tumour necrosis factor-alpha (TNF-α) production in RAW 264.7 cells. RESULTS: The results of in vitro studies revealed that derivatives 3d, 3e, 3L, and 3o are comparable to that of the oleanolic acid on the inhibition of TNF-α and IL-6 release. However, derivative 3L was identified as the most potent inhibitor of IL-6 (77.2%) and TNF-α (75.4%) when compared to parent compound, and compounds 3a (77.18%), 3d (71.5%), and 3e (68.8%) showed potent inhibition of NO than oleanolic acid (65.22%) at 10µM. Besides, from docking score and Cyscore analysis analogs (3e, 3L, 3n) showed greater affinity towards TNF-α and IL-1ß than dexamethasone. CONCLUSION: Herein, we report a series of 15 new arylidene derivatives of oleanolic acid by Claisen Schmidt condensation reaction. All the compounds synthesized were screened for their anti-inflammatory activity against NO, TNF-α and IL-6. From the data, it was evident that most of the compounds exhibited better anti-inflammatory activity.

Synthesis and biological evaluation of arylidene analogues of Meldrum's acid as a new class of antimalarial and antioxidant agents.

A series of arylidene analogues of Meldrum's acid were synthesized and evaluated for in vitro antimalarial and antioxidant activities for the first time. The influence of various physico-chemical parameters such as dielectric constant (epsilon), donor number (DN), acceptor number (AN), hydrogen bond donor (HBD), hydrogen bond acceptor (HBA), and solubilizing power of the solvents on Meldrum's acid anion generation and thus on promoting the Knoevenagel condensation of Meldrum's acid with aryl aldehydes has been discussed. Five compounds 9l, 9m, 9n, 9r, and 9s were found to be most active against Plasmodiumfalciparum with IC(50) values in the range of 9.68-16.11 microM. Compound 9l exhibited the most potent antimalarial activity (IC(50) 9.68 microM). The compounds were also found to possess antioxidant activity when tested against DPPH and ABTS free radicals.

Anti-inflammatory, cyclooxygenase (COX)-2, COX-1 inhibitory, and free radical scavenging effects of Rumex nepalensis.

Evaluation of the topical anti-inflammatory activity of chloroform and ethyl acetate extracts of RUMEX NEPALENSIS roots in a TPA-induced acute inflammation mouse model demonstrated a significant reduction in ear edema. The extracts were further tested on purified enzymes for COX-1 and COX-2 inhibition to elucidate their mechanism of action, and a strong inhibition was observed. Six anthraquinones and two naphthalene derivatives were isolated from the ethyl acetate extract. Among the isolated compounds, emodin was found to be a potent inhibitor with slight selectivity towards COX-2, and nepodin exhibited selectivity towards COX-1. Emodin, endocrocin, and nepodin also exhibited significant topical anti-inflammatory activity in mice. Interestingly, nepodin showed better radical scavenging activity than trolox and ascorbic acid against DPPH and ABTS radicals. The strong radical scavenging activity of chloroform and ethyl acetate extracts could be explained by the presence of nepodin as well as by the high phenolic content of the ethyl acetate extract. Thus, the anti-inflammatory effect of R. NEPALENSIS roots was assumed to be mediated through COX inhibition by anthraquinones and naphthalene derivatives and through the radical scavenging activities of naphthalene derivatives.

Role of environmental pollutants in Alzheimer's disease: a review.

Neurodegenerative disorders are commonly erratic influenced by various factors including lifestyle, environmental, and genetic factors. In recent observations, it has been hypothesized that exposure to various environmental factors enhances the risk of Alzheimer's disease (AD). The exact etiology of Alzheimer's disease is still unclear; however, the contribution of environmental factors in the pathology of AD is widely acknowledged. Based on the available literature, the review aims to culminate in the prospective correlation between the various environmental factors and AD. The prolonged exposure to the various well-known environmental factors including heavy metals, air pollutants (particulate matter), pesticides, nanoparticles containing metals, industrial chemicals results in accelerating the progression of AD. Common mechanisms have been documented in the field of environmental contaminants for enhancing amyloid-ß (Aß) peptide along with tau phosphorylation, resulting in the initiation of senile plaques and neurofibrillary tangles, which results in the death of neurons. This review offers a compilation of available data to support the long-suspected correlation between environmental risk factors and AD pathology. Graphical abstract .

Recent developments in anti-inflammatory natural products.

Many of the inflammatory diseases are becoming common in aging society throughout the world. The clinically used anti-inflammatory drugs suffer from the disadvantage of side effects and high cost of treatment (in case of biologics). Alternative to these drugs are traditional medicines and natural products, which offer a great hope in the identification of bioactive lead compounds and their development into drugs for treating inflammatory diseases. Since ancient times traditional medicines and phytopharmaceuticals are being used for the treatment of inflammatory and other disorders. The present review article describes anti-inflammatory natural products derived from plants and marine sources reported during last decade. The compounds described belong to different chemical classes such as alkaloids, steroids, terpenoids, polyphenolics, phenylpropanoids, fatty acids and lipids, and various miscellaneous compounds. The attempt is also being made to enumerate the possible leads, e.g. curcumin, resveratrol, baicalein, boswellic acid, betulinic acid, ursolic acid, and oleanolic acid, for further development with the help of structure-activity relationship (SAR) studies and their current status. In addition SAR studies carried out on the anti-inflammatory activity of flavonoid compounds and clinical studies performed on anti-inflammatory natural products are also discussed.