Nutritional characteristics of Stereospermum chelonoides (L.f.) DC., an underutilized edible wild fruit of dietary interest.

Malnutrition and hunger is a serious global issue, however, wild fruits possess the potential of combatting it being rich in nutrients. Stereospermum chelonoides (L.f.) DC., commonly known as "Patala" in Ayurvedic text, is a large wild tree bearing edible, yet, underutilized fruits consumed by the locals in Western parts of India and neighboring countries. The present study focuses on the nutritional profile of S. chelonoides fruit along with quantification of bioactive constituents using RP-HPLC-PDA and evaluation of in-vitro anti-oxidant and, anti-microbial activity. The fruit was found rich in nutritional composition having protein (2.41 % ± 0.007), fibre (3.46 % ± 0.02) and carbohydrate (90.19 % ± 1.73) with energy value of 368.2 ± 3.94 Kcal/100g. The elemental analysis of fruit resulted in macronutrients Ca, Mg and Na and micronutrients Fe, Mn, Zn, and Cu in amounts comparable to common marketed fruits. The RP-HPLC-PDA analysis revealed the presence of six phenolic compounds in all 3 extracts made from the fruit in which highest amount are present in hydro-alcoholic extract. All the extracts exhibited potent antioxidant activity evaluated through DPPH assay and oxygen radical absorbing capacity (ORAC), with highest activity in hydro-alcoholic extract. All the analyzed extracts also exhibited potent inhibition, against four human pathogens namely Pseudomonas aeruginosa, Vibrio cholerae, Escherichia coli, and Shigella flexneri. Therefore, it is evident from the study that the fruit of S. chelonoides has immense potential as a nutraceutical supplement and may help in the management of nutrient deficiency and malnutrition among rural and tribal communities.

Anti-rheumatic potential vis-à-vis aconitine and hypaconitine content analysis in different Aconitum spp. from Sikkim Himalayas (India).

Aconitum spp. are important medicinal plants mentioned in Ayurveda as Ativisa or Vatsanabha. The present study aims to evaluate anti-rheumatic potential in seven Aconitum species and correlation with aconitine and hypaconitine content. Anti-rheumatic potential was analyzed through in vitro xanthine oxidase inhibition, anti-inflammatory and ROS scavenging assays; and quantification of aconitine and hypaconitine with RP-HPLC method validated as per ICH guidelines. The findings reveal that A. palmatum possessed the most promising response (IC50 =12.68±0.15 µg/ml) followed by A. ferox (IC50 =12.912±1.87 µg/ml) for xanthin oxidase inhibition. We observed a wide variation in aconitine and hypaconitine content ranging from 0.018 %-1.37 % and 0.0051 %-0.077 % respectively on dry weight basis. Aconitine and hypaconitine showed moderate positive correlation (r=0.68 and 0.59 respectively) with anti-rheumatic potential. The study identifies potential alternative species of Aconitum that can help in sustainable availability of quality raw material.

Nutritional characterization of an underutilized legume Entada rheedii Spreng. seeds and validation of its folklore uses.

Entada rheedii seeds are a rich source of protein (23.99% ± 0.07), starch (42.04% ± 0.05) and potassium (1670.15 ppm ± 116.732). HPTLC-UV analysis (seeds) reveals galactose in considerable amount, that is, 2.60% ± 0.008. Additionally, the species is low in fat and anti-nutrient metabolites like tannin. Interestingly, the proximates in Entada seeds was found comparable with the commonly consumed legumes like cowpea, green gram, and so on. The species exhibits promising anti-radical, anti-inflammatory and anti-diabetic activity. Data advocates the folklore use of E. rheedii seeds and can be a promising alternative source of dietary nutrition, fortified with medicinal value. Standardization and validation of scientific knowledge will bring such underutilized, low-cost legumes into daily dietary intake and are a promising source for Protein-Energy-Malnutrition.

In silico guided in vitro study of traditionally used medicinal plants reveal the alleviation of post-menopausal symptoms through ERß binding and MAO-A inhibition.

The slumping level of estrogen and serotonin in menopausal women is directly associated with the occurrence of menopausal symptoms where, estrogen receptor-ß (ERß) and monoamine oxidase-A (MAO-A) are directly involved. The present investigation aimed for validation of promising plants traditionally used to alleviate menopausal symptoms with ERß mediated MAO-A inhibition potential through in silico disease-target network construction using Cytoscape plugins followed by molecular docking of phytomolecules through AutoDock vina. ADMET parameters of identified bioactive phytomolecules were analysed through swissADME and ProTox II. The efficacy of promising plant leads was further established through in vitro ERß competitive binding, MAO-A inhibition, enzyme kinetics and free radical quenching assays. In silico analysis suggested glabrene (ΔG = -9.7 Kcal/mol) as most promising against ERß in comparison to 17ß-estradiol (ΔG = -11.4 Kcal/mol) whereas liquiritigenin (ΔG = -9.4 Kcal/mol) showed potential binding with MAO-A in comparison to standard harmine (ΔG = -8.8 Kcal/mol). In vitro analysis of promising plants segregated Glycyrrhiza glabra (IC50 = 0.052 ± 0.007 µg/ml) as most promising, followed by Hypericum perforatum (IC50 = 0.084 ± 0.01 µg/ml), Trifolium pratense (IC50 = 0.514 ± 0.01 µg/ml) and Rumex nepalensis (IC50 = 2.568 ± 0.11 µg/ml). The enzyme kinetics of promising plant leads showed reversible and competitive nature of inhibition against MAO-A. The potency of plant extracts in quenching free radicals was at par with ascorbic acid. The identified four potent medicinal plants with ERß selective, MAO-A inhibitory and free radical quenching abilities could be used against menopausal symptoms however, finding needs to be validated further for menopausal symptoms in in vivo conditions for drug development.Communicated by Ramaswamy H. Sarma.

Docking experiments suggest that gloriosine has microtubule-targeting properties similar to colchicine.

Gloriosine, the predominant metabolite of Gloriosa superba L., shares chemical properties with colchicine. We analyze the microtubule-binding affinity of gloriosine at the colchicine binding site (CBS) using an in silico-in vivo approach. The In silico docking of gloriosine showed a binding score of (-) 7.5 kcal/Mol towards ß-tubulin at CBS and was validated by overlapping the coupling pose of the docked ligand with co-crystallized colchicine. 2D plots (Ligplot +) showed > 85% overlap between gloriosine and colchicine. The ADMET profile of gloriosine was in accordance with Lipinski's rule of five. Gloriosine belongs to class II toxicity with anLD50 value of 6 mg/kg. In vivo and transmission electron microscopy studies revealed that gloriosine induces abnormalities in cell division such as condensed chromosomes in C-metaphase and enlarged nucleus with increased nuclear material. Gloriosine treated cells exhibited mitotic index of about 14% compared to control of 24% and high anti-proliferative activity i.e. 63.94% cell viability at a low concentration (0.0004 mg/ml). We conclude that gloriosine has a strong affinity for ß-tubulin at CBS and thus can be used as a colchicine alternative in cytology and other clinical conditions.

Nutritional potential of an edible terrestrial orchid Eulophia nuda LINDL and validation of its traditional claim in arthritis.

ETHNO PHARMACOLOGICAL RELEVANCE: Eulophia nuda, locally known as "Amarkand" is an edible orchid, traditionally used as food and ethnomedicine in arthritis, as a blood purifier, vermifuge, in bronchitis, scrofulous glands etc. AIM: The present study focuses on the proximate-nutrient analysis, metabolic profiling of bioactive phenolic acids (PA's) and validation of anti-arthritic activity in E. nuda. MATERIALS: The proximate, nutrition and element (macro-micro) content were evaluated as per standard protocols. The anti-arthritic activity was evaluated via different Invitro models and bioactive phenolics were quantified through calibrated HPLC-UV (PDA) method, as per ICH guidelines. RESULTS: The species contains a considerable amount of proximate i.e. ash, fiber, crude alkaloid, total phenolics, and flavonoid. It is a rich source of macro-micro nutrients, carbohydrates and energy, at par with conventional cereals and super-foods like finger millet, foxtail millet etc. It also contains seven PA's viz. gallic acid, protocatechuic acid, caffeic acid, syringic acid, vanillin acid, ferulic acid and quercetin. The PA's content varies from 4.00 to 83.50 µg/ml. The anti-arthritic potential of the plant extract based on several in-vitro-models showed a promising inhibitory effect on inflammation and uric acid synthesis. CONCLUSION: The study scientifically validates the traditional claims of this traditional orchid as food and ethnomedicine. The species can be commercially explored as a supplement to combat nutritional deficiency among rural communities.

Impact of seasonal variation on four labdane-type diterpenoids in Coleus forskholii Briq.

The present study has been planned to evaluate the impact of seasonal variation in labdane-type diterpenoids namely isoforskolin, forskolin, 1,9-dideoxyforskolin and 1-deoxyforskolin in Coleus forskholii (roots). The plant samples were harvested in different seasons from our experimental field located at CSIR-NBRI garden, Lucknow (India) and metabolite contents were estimated through validated high performance thin layer chromatography (HPTLC) method. The HPTLC plate was developed in tertiary mobile phase of toluene-ethyl acetate-methanol (8.5-1-0.05 v/v) for separation of all the four metabolites. The metabolite content viz. isoforskolin, forskolin, 1,9-dideoxyforskolin and 1-deoxyforskolin varies from 0.0247% to 0.198%, 0.238 to 0.730%, 0.056 to 0.161% and 0.0401 to 0.332% on dry weight basis respectively. The maximum content of metabolites was recorded in winter season and was found optimum for harvesting of C. forskholii roots. Optimization of harvesting season for this industrially valuable medicinal plant will lead to sustainable sources of good quality raw material to herbal drug industry.

Evaluation of Coscinium fenestratum (Goetgh.) Colebr. stem extracts for urolithiasis and quantification of bioactive alkaloids to validate the traditional claims.

Coscinium fenestratum (Goetgh.) Colebr. is widely used for urinary disorders and kidney stones by ethnic communities in southern India. The species is documented in various ancient Indian Ayurvedic literatures having therapeutic use in 'Ashmari' i.e., urolithiasis. The present study aims at validation of in-vitro anti-urolithiatic potential of various extracts of C. fenestratum stem along with identification and quantification of major bioactive alkaloids, i.e., berberine and palmatine through HPTLC and LC-MS/MS. Water extract showed maximum anti-urolithiatic activity which on further kinetic analysis, showed concentration dependent inhibitory delay in nucleation and aggregation of calcium oxalate crystals. Berberine and palmatine were quantified with maximum content in methanolic extract (0.478 ± 0.003 and 0.0358 ± 0.001) followed by chloroform and petroleum ether extracts. The study validates ethnobotanical use of C. fenestratum as anti-urolithiatic agent. Further, species can also be explored as a substitute for Berberis spp. for the alkaloid metabolites i.e., berberine and palmatine.

Study on Chemotypic Variability of Coleus forskohlii Briq., Samples Collected from Different Phytogeographical Locations of India and Evaluation of Its Inhibitory Potential.

Coleus forskohlii Briq. is an important medicinal herb, endowed with a wide range of medicinal properties against the variety of ailments. Seven germplasm of C. forskohlii collected from different phyto-geographical locations and identification of elite chemotype was performed with the help of high performance thin layer chromatography. Data of soil analysis correlated with the bioactive compounds and inhibitory potential of the species. Quantification of forskolin and its isomer (iso-forskolin) content were done in all the collected samples of C. forskohlii, which revealed a wide range of variations, varying from 1.15-0.004% and 0.0091 to 0.1077% per dry weights basic, respectively. Variation in the bioactive content may be due to the soil nature and environmental factors. Soil analysis of collected samples demonstrated that there is significant variation in available NPK and micronutrient content and may be reasoned for existing chemotypic variability. In vitro biological activity (antioxidant and antidiabetic) analyses were performed, which reveals that germplasms have a high amount of forskolin and iso-forskolin, both show more activity. The aim of this study was to elucidate the effect of elicitors and precursors on the production of bioactive compounds and identification of best elite germplasm among the populations, to provide basic lead to the industry for commercial exploitability including its location-specific commercial cultivation.

Influence of Soil Variation on Diosgenin Content Profile in Costus speciosus from Indo-Gangetic Plains.

Costus speciosus is a rich source of commercially important compound Diosgenin, distributed in different regions of India. The present investigation was aimed to quantify diosgenin through High Performance Thin Layer Chromatography in 34 germplasms of Costus speciosus and also to identify the superior sources and to correlate the macronutrients of rhizospheric soil. The starch content varied in microscopic examination and correlated inversely (r=-0.266) with diosgenin content. Findings revealed that the extraction process with acid hydrolysis yielded higher diosgenin content (0.15-1.88 %) as compared to non-hydrolysis (0.009-0.368 %) procedure. Germplasms from Uttar Pradesh (NBCS-4), Jharkhand (NBCS-39) and Bihar (NBCS-2) were identified as elite chemotypes based on hierarchical clustering analysis. The phosphorous content of respective rhizospheric soil correlated positively (r=0.742) with diosgenin content. Findings of present study are useful to identify the new agrotechniques. The elite germplasms can also be used as quality planting material for large scale cultivation in order to assure a sustained supply to the herbal drug industry.

Chemodiversity and molecular variability in the natural populations (India) of Gloriosa superba (L.) and correlation with eco- geographical factors for the identification of elite chemotype(s).

Gloriosa superba L. has economic significance due to colchicine, a bioactive compound used for gout. In present study metabolic and molecular variability in natural population of species was analyzed and correlated with edaphic and climatic factors. Thirty populations (wild) of G. superba were mapped from 10 different eco-regions of India at an elevation range of 10-1526 m, having no morphotypic variations. The two known biologically active alkaloids colchicine (ranged from 0.015-0.516%) and gloriosine (0.19-0.44%) were significantly varied (p < 0.05) among populations, leading to the identification of four elite chemotypes. Molecular variability from ISSR data divides the population in different sub clusters at intra-specific level, presenting the high similarity percentage with bootstrap value of 66-100%. Principal component analysis (PCA) revealed that elite chemotypes are related to temperature, precipitation and aridity gradient. The rhizospheric soil selenium was significantly correlated with colchicine content in G. superba.

Simultaneous Quantification of Pharmacologically Active Alkaloid Metabolites Colchicine and Gloriosine in Gloriosa Superba L. collected from Western Ghats (India) and Adjoining Areas for the Identification of Elite Chemotype(s).

BACKGROUND: Gloriosa superba is a valuable Ayurvedic medicinal plant and is in high demand in the world market for its colchicine content, which is used to treat gout. OBJECTIVE: The study aims (1) to record the metabolic variations in major bioactive metabolites, colchicine and gloriosine, in the natural populations of G. superba from Western Ghats and adjoining areas in India and (2) to develop HPTLC protocol for the identification of elite chemotypes of species and regulation of quality raw material, extract, and finished material. METHOD: Simultaneous quantification of colchicine and gloriosine in 22 natural populations through validated HPTLC as per ICH guidelines. RESULTS: Colchicine and gloriosine were identified at Rf 0.51 ± 0.03 and 0.41 ± 0.05 and the content varied from 0.021 to 0.86% and 0.003 to 0.198%. The method was found linear at a concentration range of 0.1-0.7 µg/spot, and LOD (3.3 σ/S) and LOQ (10 σ/S) was 0.71 and 2.16 µg/spot. The method was precise in the concentration range of 100-300 ng/spot, with 98.29% and 101.12% recovery (% RSD) for colchicine and gloriosine. Subsequently, four elite chemotypes were identified based on cluster analysis of metabolite content. CONCLUSION: The developed HPTLC method is linear, accurate, precise, and robust for simultaneous quantification of colchicine and gloriosine metabolite(s). Intraspecific metabolic variation was significant among the collected population, leading to the identification of four elite chemotypes. HIGHLIGHTS: Colchicine is an industrially viable metabolite and is therefore quintessential to the development of an economical and analytical method to regulate the quality of raw material, extract, and finished products.

In-silico efficacy of potential phytomolecules from Ayurvedic herbs as an adjuvant therapy in management of COVID-19.

The recent COVID-19 outbreak caused by SARS-CoV-2 virus has sparked a new spectrum of investigations, research and studies in multifarious directions. Efforts are being made around the world for discovery of effective vaccines/drugs against COVID-19. In this context, Ayurveda, an alternative traditional system of medicine in India may work as an adjuvant therapy in compromised patients. We selected 40 herbal leads on the basis of their traditional applications. The phytomolecules from these leads were further screened through in-silico molecular docking against two main targets of SARS-CoV-2 i.e. the spike protein (S; structural protein) and the main protease (MPRO; non-structural protein). Out of the selected 40, 12 phytomolecules were able to block or stabilize the major functional sites of the main protease and spike protein. Among these, Ginsenoside, Glycyrrhizic acid, Hespiridin and Tribulosin exhibited high binding energy with both main protease and spike protein. Etoposide showed good binding energy only with Spike protein and Teniposide had high binding energy only with main protease. The above phytocompounds showed promising binding efficiency with target proteins indicating their possible applications against SARS-CoV-2. However, these findings need to be validated through in vitro and in vivo experiments with above mentioned potential molecules as candidate drugs for the management of COVID-19. In addition, there is an opportunity for the development of formulations through different permutations and combinations of these phytomolecules to harness their synergistic potential.

Variability in alkaloid and phenolic content vis-a-vis antigout potential among the natural population of Gloriosa superba (L.) collected from Central India.

The variation in alkaloid metabolites (colchicine and gloriosine) was found significant in the nine germplasms of G. superba (L.), collected from Central India. The maximum content of colchicine and gloriosine was in NBG-15 (Chitrakoot, M.P) and NBG-13 (Bheraghat, M.P). The phenolic acids viz. quercetin and kaempferol was first ever quantified in G. superba tuber. Cluster analysis on chemical variability (colchicine and gloriosine content) results in the identification of three elite germplasm(s). The radical scavenging potential was also found promising in the selected elite germplasm viz. NBG-13, NBG-14 and NBG-15. Further, the protein denaturation potential of elite chemotypes was found at par with standard colchicine. The study will aid in site specific exploration of high metabolite yielding chemotype(s) with validated pharmacological action to meet out the industrial demands. This will also promotes the commercial cultivation of species for socio economical upliftment in the area having similar phyto geographical conditions.

Chemotaxonomic studies on natural population of Gloriosa superba (L.) collected from Gangetic plain (India) and their invitro antigout activity for the identification of elite germplasm(s).

ETHNOPHARMACOLOGICAL RELEVANCE: Gloriosa superba L. (Colchicaceae) is used in the treatment of gout and rheumatism as a traditional medicine dates back to 1810. It has also been used as ethnobotanical and folklore medicine to induce abortion/vaginal poison. AIM OF STUDY: The present study was carried out to identify the chemical variation existing in the major alkaloid metabolite (colchicine) in a threatened species, Gloriosa superba L. and is correlated with invitro antigout activity. MATERIAL AND METHOD: The samples (tuber) were collected from their natural locations in Gangetic plain of India. HPLC-PDA quantification of colchicine was done on C18 column at 245 nm and invitro antigout activity was analyzed by inhibition of protein denaturation, DPPH and Hydroxyl radical scavenging assay. RESULTS: The colchicine content within the 29 samples ranges from 0.021 to 0.665% and the maximum contents was in NBG-10 from Kanth (U.P). Such high colchicine (0.665%) containing natural population of G. superba is reported for the first time in Indian population. Four chemotypes viz. NBG-10, NBG-120, NBG-126 and NBG-88 were selected on the basis of colchicine content for invitro antigout activity. NBG-10 was separated from rest of the population exhibiting the most promising activity with high colchicine content. CONCLUSION: The outcomes will be helpful in the identification of elite chemotype for herbal product development and quality check of metabolites in raw material. The study will also support the site-specific commercial cultivation to meet out the industrial demand as well as income generation to farmers.

Aspirin & clopidogrel non-responsiveness & its association with genetic polymorphisms in patients with myocardial infarction.

Background & objectives: Cytochrome P450, P2Y 12, cyclooxygenase-1 (COX1) and glycoprotein V1 (GPVI) gene polymorphisms are known to affect patient responsiveness towards aspirin and clopidogrel dual antiplatelet therapy (DAPT). The present study was undertaken to identify aspirin and clopidogrel non-responsiveness and its association with genetic polymorphism in patients with myocardial infarction (MI). Methods: A total of 207 MI patients who were on DAPT, were included. The DAPT non-responsiveness was determined by light transmittance aggregometry using arachidonic acid and adenosine diphosphate and high platelet reactivity by collagen. Platelet activation biomarkers, thromboxane B2 (TxB2)andsoluble CD40 ligand (sCD40L) were measured in plasma. Patient compliance was checked by estimating drug and its metabolite levels (aspirin and clopidogrel) in plasma using liquid chromatography-mass spectrometry/mass spectrometry. Genomic DNA was extracted, amplified by polymerase chain reaction and subsequently sequenced to identify CYP450, P2Y 12, COX1 and GPVI gene polymorphisms. Results: Of the 207 patients, 32 were non-responders. The DAPT non-responsiveness was found in 15.5 per cent patients. The non-responsiveness showed a significant and an independent association with gender [odds ratio (OR)=0.18, 95% confidence interval (CI)=0.01-0.78, P=0.023], TxB2(OR=1.00, 95% CI=1.00-1.01, P=0.013), CYP2C19*2 G>A (OR=3.33, 95% CI=1.04-10.69, P=0.044) and GPVI T>C (OR=0.23, 95% CI=0.08-0.67, P=0.007) after adjusting the demographic, clinical and genetic confounding factors when assessed between non-responder and responder compliant patients. Interpretation & conclusions: The study showed a significant association of genetic polymorphisms (CYP2C19*2 G>A and GPVI T>C) with DAPT non-responsiveness in MI patients. The findings of this study need further validation in a large cohort of patients with clinical follow up.

Household fuel use and biomarkers of inflammation and respiratory illness among rural South African Women.

Though literature suggests a positive association between use of biomass fuel for cooking and inflammation, few studies among women in rural South Africa exist. We included 415 women from the South African Study of Women and Babies (SOWB), recruited from 2010 to 2011. We obtained demographics, general medical history and usual source of cooking fuel (wood, electricity) via baseline questionnaire. A nurse obtained height, weight, blood pressure, and blood samples. We measured plasma concentrations of a suite of inflammatory markers (e.g., interleukins, tumor necrosis factor-α, C-reactive protein). We assessed associations between cooking fuel and biomarkers of inflammation and respiratory symptoms/illness using crude and adjusted linear and logistic regression models. We found little evidence of an association between fuel-use and biomarkers of inflammation, pre-hypertension/hypertension, or respiratory illnesses. Though imprecise, we found 41% (95% confidence interval (CI) = 0.72-2.77) higher odds of self-reported wheezing/chest tightness among wood-users compared with electricity-users. Though studies among other populations report positive findings between biomass fuel use and inflammation, it is possible that women in the present study experience lower exposures to household air pollution given the cleaner burning nature of wood compared with other biomass fuels (e.g., coal, dung).

Simultaneous Quantification of Forskolin and Iso-Forskolin in Coleus forskohlii (Wild.) Briq. and Identification of Elite Chemotype, Collected from Eastern Ghats (India).

BACKGROUND: Coleus forskohlii is a well-known industrially important medicinal plant, for its high forskolin content. OBJECTIVE: A simple, selective, and sensitive high-performance thin layer chromatography (HPTLC) method was developed and validated for simultaneous quantification of forskolin and iso-forskolin in C. forskohlii germplasm collected from the Eastern Ghats, India. MATERIALS AND METHODS: Chromatographic separation of the targeted marker(s) was obtained on precoated silica plates using toluene: ethyl acetate: methanol (90:30:0.5, v/v/v) as the mobile phase. RESULTS: Densitometric quantification of forskolin and iso-forskolin was carried out at 545 nm. Forskolin and iso-forskolin were identified by comparing the ultraviolet spectra of standard and sample track at Rf of 0.64 ± 0.02 and 0.36 ± 0.01, after derivatization with anisaldehyde sulfuric acid reagent. The linearity of both the analytes was obtained in the range of 300-1200 ng/spot with the regression coefficient (R2) of 0.991 and 0.986. Recovery of analyte (s) at three levels, namely, 100, 150, and 200 ng/spot was found to be 100.46% ± 0.29%, 99.64% ± 0.33%, 100.02% ± 0.76% and 99.76% ± 0.62%, 99.56% ± 0.35%, 100.02% ± 0.22%, respectively, for forskolin and iso-forskolin. The content of forskolin and iso-forskolin varies from 0.046% to 0.187% and 0.002% to 0.077%, respectively (dry weight basis), the maximum content of both the markers was found in NBC-31, from Thakurwada, Maharashtra. CONCLUSION: The developed HPTLC method was linear, accurate, and reliable as per the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. The study aids in the identification of elite chemotype for commercial prospection of industrially viable medicinal crop. SUMMARY: 12 Samples are collected from different locations of the eastern ghat regionsQuantification of two major marker forskolin and iso forskolinThe maximum content of both the markers was found in NBC -31, from Thakurwada, MaharashtraIdentification of elite chemotype of collected samples may be useful for commercial prospection in industries.

Anti-thrombotic efficacy of S007-867: Pre-clinical evaluation in experimental models of thrombosis in vivo and in vitro.

Pharmacological inhibition of platelet collagen interaction is a promising therapeutic strategy to treat intra-vascular thrombosis. S007-867 is a novel synthetic inhibitor of collagen-induced platelet aggregation. It has shown better antithrombotic protection than aspirin and clopidogrel with minimal bleeding tendency in mice. The present study is aimed to systematically investigate the antithrombotic efficacy of S007-867 in comparison to aspirin and clopidogrel in vivo and to delineate its mechanism of action in vitro. Aspirin, clopidogrel, and S007-867 significantly reduced thrombus weight in arterio-venous (AV) shunt model in rats. In mice, following ferric chloride induced thrombosis in either carotid or mesenteric artery; S007-867 significantly prolonged the vessel occlusion time (1.2-fold) and maintained a sustained blood flow velocity for >30 min. Comparatively, clopidogrel showed significant prolongation in TTO (1.3-fold) while aspirin remained ineffective. Both S007-867 and aspirin did not alter bleeding time in either kidney or spleen injury models, and thus maintained hemostasis, while clopidogrel showed significant increase in spleen bleeding time (1.7-fold). The coagulation parameters namely thrombin time, prothrombin time or activated partial thromboplastin time remained unaffected even at high concentration of S007-867 (300 µM), thus implying its antithrombotic effect to be primarily platelet mediated. S007-867 significantly inhibited collagen-mediated platelet adhesion and aggregation in mice ex-vivo. Moreover, when blood was perfused over a highly thrombogenic combination of collagen mimicking peptides like CRP-GFOGER-VWF-III, S007-867 significantly reduced total thrombus volume or ZV50 (53.4 ±â€¯5.7%). Mechanistically, S007-867 (10-300 µM) inhibited collagen-induced ATP release, thromboxane A2 (TxA2) generation, intra-platelet [Ca+2] flux and global tyrosine phosphorylation including PLCγ2. Collectively the present study highlights that S007-867 is a novel synthetic inhibitor of collagen induced platelet activation, that effectively maintains blood flow velocity and delays vascular occlusion. It inhibits thrombogenesis without compromising hemostasis. Therefore, S007-867 may be further developed for the treatment of thrombotic disorders in clinical settings.