Immunomodulatory efficacy of Cousinia thomsonii C.B. Clarke in ameliorating inflammatory cascade expressions.

ETHNOPHARMACOLOGICAL RELEVANCE: Cousinia thomsonii is traditionally known for treating various diseases including joint pain, swelling, body ache, asthma, dermatitis, cough and arthritis. AIM OF THE STUDY: This study employs lipopolysaccharide induced inflammatory wistar-rat model to evaluate efficacy of Cousinia thomsonii active-extracts on the expression of crucial inflammatory markers viz. iNOS, PPAR-γ, Rel-A, COX-2 and serum analysis of CRP. MATERIALS AND METHODS: Methanol and aqueous extracts were administered orally at 25, 50, 100 mg/kg doses for 21 days. Serum was collected on 22nd day and rats were sacrificed to extract paw tissues. Dexamethasone (0.5 mg/kg) served as positive control. Immunoblotting and qPCR was used for expression analysis of iNOS, PPAR-γ, Rel-A, COX-2 respectively. ELISA was employed for evaluating CRP levels. Discovery-studio and Auto-Dock-Vina were used to check docking interactions of various identified compounds. RESULTS: Both extracts caused dose-dependent decline in iNOS, Rel-A, COX-2 and CRP levels, while there was a dose-dependent increase in PPAR-γ expression. Methanol extract dominated immunomodulatory potential as compared with the aqueous extract. The results of the GCMS revealed the presence of ten compounds. Some of these compounds include 1-Octacosanol, Ethyl Linoleate, 1-Heptacosanol, 1-Hexadecanol, 1-Dodecanol and Behenic alcohol having strong anti-inflammatory, antimicrobial, anti-acne and anti-viral activities. Molecular Docking scores were calculated between each target protein and selected compounds. The best affinity/interactions were observed between 1-Octacosanol towards iNOS, PPAR-γ, Rel-A, COX-2 and CRP with binding energy of -10.4, -11.1, -8.6, -9.9 and -7.9 (kcal/mol) respectively. These compounds may act as strong inhibitors for iNOS, Rel-A, COX-2 and CRP or as agonists for PPAR-γ; thereby inducing anti-inflammatory/immuno-modulatory activities. CONCLUSIONS: The results indicate that Cousinia thomsonii contains therapeutically active compounds and thus could serve as potential therapeutic regimen against diverse inflammatory diseases.

Habitat suitability, range dynamics, and threat assessment of Swertia petiolata D. Don: a Himalayan endemic medicinally important plant under climate change.

In the current era of the anthropocene, climate change is one of the main determinants of species redistribution and biodiversity loss. Worryingly, the situation is alarming for endemic and medicinally important plant species with a narrow distributional range. Therefore, it is pivotal to inspect the influence of accelerated climate change on medicinally important threatened and endemic plant species. Using an ensemble approach, the current study aims at modelling the present distribution and predicting the future potential distribution coupled with the threat assessment of Swertia petiolata-a medicinally important endemic plant species in the Himalayan biodiversity hotspot. Our study revealed that under current climatic scenarios, the suitable habitats for the species occur across the western Himalayan region which includes the north-western Indian states (Jammu and Kashmir, Himachal Pradesh, and southern Uttarakhand), northern Pakistan, and north-western Nepal. Also, temperature seasonality (BIO4) and precipitation seasonality (BIO15) are the most significant bioclimatic variables determining the distribution of S. petiolata. Furthermore, the study projected a reduction in the suitable habitats for the species under future changing climatic scenarios with a reduction ranging from - 40.298% under RCP4.5 2050 to - 83.421% under RCP8.5 2070. Most of the habitat reduction will occur in the western Himalayan region. In contrast, some of the currently unsuitable Himalayan regions like northern Uttarakhand will show increasing suitability under climate change scenarios. The current study also revealed that S. petiolata is classified as Near Threatened (NT) following the IUCN criterion B. Hopefully, the present study will provide a robust tool for predicting the cultivation hotspots and devising scientifically effective conservation strategies for this medicinally important plant species in the Himalaya and similar environments elsewhere in the world.

Medicinal importance of Papra (Podophyllum hexandrum Royle) in Unani System of Medicine.

Podophyllum hexandrum Royle [=Sinopodophyllum hexandrum (Royle) T.S. Ying] is an important, endemic medicinal plant species of Himalaya. It is used in Unani System of Medicine under the name of 'Papra'. The drug was not mentioned in previous literatures, but the first time it introduced in Unani Medicine by a great scholar Hakim Najmul Ghani. He has mentioned its uses and benefits in his classical book Khazainul Advia. In Unani Medicine the plant species has been used to treat various ailments like constipation, fever, jaundice, liver disorders, syphilis, diseases of lymph glands etc. In Kashmir Himalaya it is used to treat various diseases by local medicinemen, but now it is listed in rare drugs. Various pharmacological studies have been done such as antioxidant, antimicrobial, anti-inflammatory, antifungal, radio-protective etc., recently it has also been reported that podophyllotoxin or podophyllin can be used to treat some forms of cancers also.

Active Cousinia thomsonii Extracts Modulate Expression of Crucial Proinflammatory Mediators/Cytokines and NFκB Cascade in Lipopolysaccharide-Induced Albino Wistar Rat Model.

INTRODUCTION: Chronic inflammation is implicated in a multitude of diseases, including arthritis, neurodegeneration, autoimmune myositis, type 2 diabetes, rheumatic disorders, spondylitis, and cancer. Therefore, strategies to explore potent anti-inflammatory regimens are pivotal from a human-health perspective. Medicinal plants represent a vast unexplored treasure trove of therapeutically active constituents with diverse pharmacological activities, including anti-inflammatory properties. Herein, we evaluated Cousinia thomsonii, an edible medicinal herb, for its anti-inflammatory/immunomodulatory properties. METHODS: Soxhlet extraction was used to obtain different solvent extracts (hexane, ethyl acetate, ethanol, methanol, and aqueous extract) in increasing order of polarity. In vitro anti-inflammatory assays were performed to investigate the effects of extracts on protein denaturation, proteinase activity, nitric oxide surge, and erythrocyte-membrane stabilization. The most effective extracts, ie, ethyl acetate (CTEA) and ethanol (CTE) extracts (150-200 g) were selected for further in vivo analysis using albino Wistar rats. Wistar rats received varying concentrations of CTEA and CTE (25, 50, and 100 mg/kg) for 3 weeks, followed by a single subplantar injection of lipopolysaccharide. Dexamethasone served as positive control. Blood was obtained from the retro-orbital plexus and serum separated for estimation of proinflammatory cytokines (IL6, IL1ß, IFNγ and TNFα). Western blotting was performed to study expression patterns of crucial proteins implicated in the NFκB pathway, ie, NFκB p65, NFκB1 p50, and NFκB2 p52. Histopathological examination was done and gas chromatography-mass spectrometry (GC-MS) carried out to reveal the identity of compounds responsible for ameliorating effects of C. thomsonii. RESULTS: Among five tested extracts, CTEA and CTE showed marked inhibition of protein denaturation, proteinase activity, nitric oxide surge and erythrocyte-membrane hemolysis at 600 µg/mL (P<0.001). Both these extracts showed no toxic effects up to a dose of 2,500 mg/kg. Extracts exhibited concentration-dependent reductions in expression of IL6, IL1ß, IFNγ, TNFα, NFκB-p65, NFκB1, and NFκB2 (P<0.05). Healing effects of extracts were evident from histopathological investigation. GC-MS analysis revealed the presence of important anti-inflammatory compounds, notably stigmast-5-en-3-ol, oleate, dotriacontane, ascorbic acid, n-hexadecanoic acid, and α-tocopherol, in C. thomsonii. CONCLUSION: C. thomsonii possesses significant anti-inflammatory/immunomodulatory potential by virtue of modifying levels of proinflammatory cytokines/markers and NFκB proteins.