Fenugreek seeds, among the top functional foods have traditionally been utilized for the management of diabetes and inflammatory diseases, but the efficacy of steroidal glycoside-rich extract (Met-E) of fenugreek seeds against obesity-induced insulin resistance and inflammation is yet to be clearly elucidated. Adipocytes were used to screen the effect of aqueous (Met-A), ethanolic (Met-E), and hydro-alcoholic (Met-HA) extracts of fenugreek seeds on lipid accumulation. Met-E, the most potent extract was subjected to UHPLC analysis for identification of phytoconstituents and its anti-inflammatory effect using LPS-activated peritoneal macrophages. UHPLC analysis revealed that Met-E extract is rich in steroidal glycoside compounds and able to reduce pro-inflammatory cytokines (TNF, IL-6, IL-1β) production in LPS-activated macrophages. The beneficial effect of Met-E was further evaluated against high-fat diet (HFD) induced insulin resistance (IR) and inflammation in C57BL/6 mice. Experimental pharmacology study in mice demonstrated that oral administration of Met-E significantly reduced body weight gain, blood glucose, serum insulin, pro-inflammatory cytokines, improved lipid profile (TG, TC, LDL-C, HDL-C), and HOMA-IR value. In addition, Met-E significantly improved insulin sensitivity and glucose tolerance in comparison to in HFD mice. Met-E significantly up-regulated mRNA expression of insulin signalling pathway (IRS-1, GLUT4, AKT, PI3K) and down-regulated mRNA expression of inflammatory genes (TNF, IL-6, IL-1β, and NF-κβ). Furthermore, histopathology immunohistochemistry and western blotting studies indicated that Met-E can ameliorate the hypertrophy in adipose tissue by downregulating NF-κβ and upregulate the GLUT4 protein expression. Acute and subacute toxicity revealed the safety of the extract. Met-E, a steroidal glycoside-rich extract from fenugreek seeds alleviates obesity-induced insulin resistance via attenuation of low-grade inflammation. The result of this study suggests the suitability of Met-E, as a functional food for further investigation toward the management of obesity and related complications.

Rutin (3, 3', 4' 5 and 7-pentahydroxyflavone-3-rhamnoglucoside) is a flavonoid glycoside, found in many edible plants such as buckwheat and berries. Severe malaria is an inflammatory response triggered by oxidative stress that results in multi-organ pathologies and a high mortality rate in children and pregnant women worldwide. Rutin is recommended as a food supplement for the treatment of various diseases due to its anti-oxidative and anti-inflammatory properties, which prompted us to investigate its ameliorative effects in severe malaria pathogenesis against oxidative stress and inflammatory response using in vitro and in vivo bioassays. Rutin was examined in this work for its anti-plasmodial activity against chloroquine-sensitive and resistant Plasmodium falciparum strains, as well as its anti-oxidative and anti-inflammatory activity against LPS-stimulated macrophage cells. The in vitro data were subsequently verified in mice fed orally with rutin alone or in combination with chloroquine in Plasmodium berghei-induced malaria pathogenesis. The anti-plasmodial and anti-inflammatory properties of rutin were demonstrated in in vitro results. Apart from its anti-inflammatory and anti-oxidant effects in malaria pathogenesis, in vivo efficacy studies indicated that oral treatment with rutin reduced parasitaemia, increased mean survival time, and restored haemoglobin and glucose levels in mice at lower dose. Interestingly, both rutin and chloroquine demonstrated synergy in in vitro and in vivo experiments. The findings of the present study thus highlighted the suitability of rutin for further study in the management of drug resistant malaria in combination with standard anti-malarial drugs.

Introduction: Endophyte is considered a source of natural bioactive secondary metabolites that provides an array of bioactive lead compounds. The present study was aimed to determine the antimicrobial and anti-inflammatory potential of fungal endophytes isolated from Catharanthus roseus. Methods: A total of seven fungal endophytes crude extract were screened against bacterial pathogens. Of these, Curvularia geniculata CATDLF7 crude extract exhibited the most potent inhibitory activity against bacterial pathogens. Hence, CATDLF7 crude extract was subjected to chromatographic separation. This purification leads to the isolation of six pure compounds (1PS - 6PS). Of these, 3PS was found to be a major constituent and most effective against clinical isolates of methicillin- resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) values ranging from 100 to 200 μg/ml. Based on the spectroscopic data, 3PS was characterized as α,β- dehydrocurvularin. This compound also showed synergistic interaction with norfloxacin and reduced its MIC up to 32-folds with a fractional inhibitory concentration index (FICI) of 0.09. Results: To understand the possible antibacterial mechanism of action, α,β-dehydrocurvularin alone (100 μg/ml) exhibited efflux pump inhibitory potential by 0.84 fold decreasing in ethidium bromide (EtBr) fluorescence. In addition, α,β-dehydrocurvularin inhibited inflammatory cytokines TNF-α and IL-6 production, which is further validated by molecular docking scores -4.921 and -5.641, respectively, for understanding orientation and binding affinity. Conclusion: Overall, the results highlighted identifying bioactive compound α,β-dehydrocurvularin, which could be used as an antimicrobial and anti-inflammatory agent.

Present study was aimed to investigate the antibacterial activity, bactericidal mechanism of action, killing kinetics and anti-inflammatory activity of Isodon melissoides (Benth.) H. Hara essential oil. The gas chromatography-flame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of carvacrol (45.4%), p-cymene (11.6%) and thymol (11.3%) as major constituents of the oil. The oil displayed broad spectrum significant antibacterial activity (MIC: 0.13-8.33 ppm; MBC: 0.13->33.34 ppm) against test strains. The oil exhibited a time and dose-dependent bactericidal effect. The oil disrupted the cell membrane by changing the cell membrane permeability. The essential oil significantly decreased the overproduction of proinflammatory cytokines in LPS-induced inflammation in HaCaT cells without any cytotoxic effect. I. melissoides essential oil can be a promising alternative antimicrobial agent for the control of methicillin resistant staphylococci and other pathogenic bacteria tested, and also useful for the topical anti-inflammatory properties.

A volatile alkaloid quinoline-4-carbonitrile (QCN) was isolated from the floral extract of Quisqualis indica. Major compounds were trans-linalool oxide (1.0, 4.5%), methyl benzoate (1.0, 4.0%), 2,2,6-trimethyl-6-vinyl-tetrahydropyran-3-one (7.4, 17.8%), 2,2,6-trimethyl-6-vinyl-tetrahydropyran-3-ol (1.0, 1.2%), (E,E)-α-farnesene (29.1, 16.1%), QCN (5.7, 1.3%) in live and picked flowers, respectively. Flower compositions were altered due to change in enzymatic reaction at the time of picking. Some rearrangements of oxygenated terpenoids occurred in the process of hydrodistillation to obtain essential oil. Chemical synthesis of QCN and its selectively reduced products derived from QCN were prepared through green reaction process. The catalytic modification of QCN has produced quinoline-4-methylamine; the later compound has shown enhanced bio-activities. QCN and floral extract (absolute) have shown potential anti-inflammatory and antioxidant activities. Besides, floral absolute has shown significant anti-inflammatory and antioxidant activities due to improved QCN (19.7%) content to synergize amongst terpenoids and benzenoids as compared to the essential oil with 1.1% of QCN.

Curcuma longa L. is an important industrial crop used by medicinal and cosmetic industries in the world. Its leaves are a waste material after harvesting rhizomes. The aim of the study was to evaluate the chemical and pharmacological profile of essential oil from waste leaves of Curcuma longa (EOCl) against skin inflammation.

Chemical investigations on the fruits of Zanthoxylum armatum Roxb. (Rutaceae) led to the isolation of two new constituents characterised as 2α-methyl-2β-ethylene-3β-isopropyl-cyclohexan-1β, 3α-diol (1) and phenol-O-β-D-arabinopyranosyl-4'-(3″, 7″, 11″, 15″-tetramethyl)-hexadecan-1″-oate (2) along with known compounds m-methoxy palmityloxy benzene (3), acetyl phenyl acetate (4), linoleiyl-O-α-D-xylopyranoside (5), m-hydroxyphenoxy benzene (6) and palmitic acid (7). The chemical structures were established with the help of physical, chemical and spectroscopic methods. The anti-inflammatory potential of isolated compounds 1 and 2 was evaluated using in vitro target-based anti-inflammatory activity in LPS-stimulated primary peritoneal macrophages isolated from mice. Production of pro-inflammatory cytokines (TNF-α and IL-6) was significantly inhibited by the treatment of isolated compounds 1 and 2 in a dose-dependent manner.

Diarylheptanoids, a group of plant secondary metabolites are increasingly recognized as potential therapeutic agents. The aim of study was to ascertain the anti-inflammatory profile of diarylheptanoids from Alnus nepalensis against lipopolysaccharide (LPS)-induced inflammation in macrophages and endotoxic shock in mice. Extracts prepared from dried leaves of A. nepalensis using standard solvents were tested against LPS-induced inflammation in macrophages. Among all, butanol extract (ANB) has shown most significant inhibition of pro-inflammatory cytokines without any cytotoxicity. HPLC analysis of ANB showed the presence of diarylheptanoids. The diarylheptanoids were further isolated and tested in-vitro for anti-inflammatory activity. Treatment of isolated diarylheptanoids (HOG, ORE and PLS) was able to reduce the production and mRNA level of pro-inflammatory cytokines (TNF-α and IL-6). Furthermore, we demonstrated that it inhibited the expression of NF-kB protein in LPS-induced inflammation in macrophages. In-vivo efficacy and safety profile of ANB revealed that oral treatment of ANB was able to improve the survival rate, and inhibited the production of pro-inflammatory cytokines in serum, attenuated vital organ injury in a dose dependent manner without any toxic effect at higher dose in mice. The results suggest that diarylheptanoids from A. nepalensis can be considered as potential therapeutic candidates for the management of inflammation related diseases.

BACKGROUND:Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases risk of having a range of gastrointestinal problems. Therefore, new anti-inflammatory, analgesic, antipyretic drugs having lesser side effects are being searched all overthe world as alternatives to NSAIDs.AIMS:To evaluate the anti-inflammatory, analgesic and antipyretic profile of Ocimum sanctum root extracts.MATERIALS AND METHODS:Anti-inflammatory profile of hexane (STH), chloroform (STC), ethyl acetate (STE), butanol (STB) and water (STW) extracts of OS was carried out by using carrageenan induced paw edema. STE a most active extract was further validated in dose dependent manner for anti-inflammatory, analgesic and antipyretic activity as well as oral toxicity profile in small laboratory animals. Identification of bioactives flux and chemical signature of most active fraction STE was developed by using the high-performance liquid chromatography fingerprinting.RESULTS:An ethyl acetate fraction (STE) exhibit most potent anti-inflammatory activity followed by STB, STW, STC and STH. Dose response study of STE showed anti-inflammatory, analgesic and anti-pyretic potential in dose-dependent manner without any toxic effect at dose 2000 mg/kg. Chemical fingerprint revealed the presence of flavanoids.CONCLUSIONS:The present research revealed that STE possess anti-inflammatory, analgesic and anti-pyretic properties. However, future research is advocated to evaluate the pharmacological properties of isolated bioactive compounds.

We herein report the synthesis of diosgenin analogues from commercially available diosgenin as the starting material. The structures of newly synthesised compounds were confirmed by (1)H NMR, (13)C NMR and mass spectrometry. All analogues were evaluated for in-vitro anti-inflammatory profile against LPS-induced inflammation in primary peritoneal macrophages isolated from mice by quantification of pro-inflammatory (TNF-α, IL-6 and IL-1β) cytokines in cell culture supernatant using the ELISA technique followed by in-vitro cytotoxicity study. Among the synthesised analogues, analogue 15 [(E) 26-(3',4',5'-trimethoxybenzylidene)-furost-5en-3β-acetate)] showed significant anti-inflammatory activity by inhibiting LPS-induced pro-inflammatory cytokines in a dose-dependent manner without any cytotoxicity. Efficacy and safety of analogue 15 were further validated in an in-vivo system using LPS-induced sepsis model and acute oral toxicity in mice. Oral administration of analogue 15 inhibited the pro-inflammatory cytokines in serum, attenuated the liver and lung injury and reduced the mortality rate in sepsis mice. Acute oral toxicity study showed that analogue 15 is non-toxic at higher dose in BALB/c mice. Molecular docking study revealed the strong binding affinity of diosgenin analogues to the active site of the pro-inflammatory proteins. These findings suggested that analogue 15 may be a useful therapeutic candidate for the treatment of inflammatory diseases.