A comprehensive review on ethnomedicinal, phytochemical and pharmacological properties of genus Bistorta (L.) scop.

The genus Bistorta comprises about 43 accepted species that are widely used by local people and medicinal practitioners for the treatment of rheumatism, tuberculosis, inflammation, respiratory infection, and other diseases. The objective of this review is to present up-to-date information from the scientific literature about the phytochemistry, pharmacology, and toxicology of Bistorta. At present, there is a lack of a comprehensive review that consolidates the various scientific studies conducted on the genus Bistorta. To address this knowledge gap, a global review has been compiled on the genus Bistorta, which emphasizes ethnomedicinal uses, phytochemistry, and pharmacology. To gather information about Bistorta, relevant keywords were used to search internet databases including Google scholar, PubMed, ResearchGate, Web of Science, Europe PMC, CNKI, and Wiley Online Library. Additionally, published books that provided an overview of existing literature studies were consulted for reference purposes. Chemical structures and formulas of compounds were verified using the PubChem database and drawn using Chem Draw Ultra 6.0. The scientific nomenclature utilized in this review follows The World Flora Online and The Plant of the World Online (PoWo). A comprehensive evaluation of literature sources revealed that the genus Bistorta has been recognized for its ethnomedical properties and has been used in traditional healthcare for several millennia. Chemical analysis has identified various compounds such as phenolics, flavonoids saponins, terpenes, sterols, and coumarins which have been shown to have significant pharmacological effects such as anti-tumor, anti-inflammatory, anti-oxidant anti-rheumatic and anti-microbial properties. The pharmacological research has only partially validated the traditional and local uses of Bistorta species. Further research is required to investigate the mechanisms of the plant's active compounds, as well as its potential therapeutic applications in treating conditions like diabetes and neurodegenerative diseases. Additionally, there is no clinical evidence to provide the health benefits of these plants. To confirm the pharmacological activities, clinical efficacy, and non-toxicity of Bistorta species, more comprehensive and systematic preclinical studies, and clinical trials are needed.

Seed biology imperative for conservation and restoration of Swertia thomsonii C.B. Clarke-an endemic medicinal plant of Himalaya.

Endemic medicinal plants deserve immediate research priorities as they typically show a limited distribution range, represent few and fragmented populations in the wild and are currently facing anthropogenic threats like overharvesting and habitat degradation. One of the important aspects of ensuring their successful conservation and sustainable utilization lies in comprehending the fundamental seed biology, particularly the dormancy status and seed germination requirements of these plants. Here, we studied the seed eco-physiology and regeneration potential of Swertia thomsonii-an endemic medicinal plant of western Himalaya. We investigated the effect of different pre-sowing treatments, sowing media and sowing depth on seed germination parameters of S. thomsonii. Seeds of S. thomsonii exhibit morphophysiological dormancy (MPD), i.e. when the embryo of the seed is morphologically and/or physiologically immature. Wet stratification at 4 °C for 20 days, pre-sowing treatment with 50 ppm GA3 and pre-sowing treatment with 50 ppm KNO3 were found ideal for overcoming dormancy and enhancing the seed germination of S. thomsonii. Furthermore, seed germination and seedling survival were significantly influenced by pre-sowing treatments, sowing media and sowing depth. The percentage of seed germination and seedling survival got enhanced up to 84-86% and 73-75% respectively when seeds were pre-treated with GA3 or KNO3 and then sown in cocopeat + perlite (1:1) at a depth of 1 cm. The information obtained in the present study outlines an efficient protocol for large-scale cultivation of S. thomsonii thereby limiting the pressure of overexploitation from its natural habitats and may also help in the restoration and conservation of this valuable plant species.

Exploring morphological variability, in vitro antioxidant potential, and HR-LCMS phytochemical profiling of Phlomis cashmeriana Royle ex Benth. across different habitats of Kashmir Himalaya.

Phytochemicals are broadly acknowledged for their health-promoting effects owing to the fact of their capacity to counteract free radicals (e.g., superoxide anion radical, hydroxyl radical, hydroperoxyl radical, singlet oxygen, hypochlorite, and nitric oxide) and shield against oxidative stress induced by environmental factors. This study aimed to investigate the relationship between altitude, morphology, soil parameters, in vitro antioxidant potential and phytochemical composition of Phlomis cashmeriana collected from four different locations of Kashmir Himalaya characterized by diverse habitats and elevations. Various factors, such as extraction method, solvent polarity, and habitat conditions, can impact the quantity and efficacy of phytochemicals in plants. The aim of current study was to analyze phytochemical composition and antioxidant activity of P. cashmeriana, an important medicinal plant found in the Kashmir Himalaya region. The antioxidant activity was accessed using several assays and the plant populations were selected based on their diverse habitat features and altitudes. HR-LCMS was conducted for both below-ground and above-ground parts. Some important compounds such as, catechin, vinainsenoside, acutilobin, and kaempferol were reported for the first time from P. cashmeriana. Results showed that methanol was the most efficient solvent for extracting phytochemicals. During the current study, it was also found that the below-ground parts exhibited superior antioxidant activity compared to the above-ground parts. Notably, Site IV demonstrated the highest antioxidant potential; a positive correlation between altitude and antioxidant activity was also found. In conclusion, present research identified specific elite populations having highest antioxidant potential and are well-suited for large-scale cultivation of P. cashmeriana.

Variability in morphology, phytochemicals and antioxidant activity in Bistorta amplexicaulis (D. Don) Greene populations under variable habitats and altitudes.

Phytochemicals have become significantly important for scientific research since these possess incredibly remarkable health benefits, especially antioxidant potential to scavenge free radicals and combat the harmful effects of oxidative stress caused by adverse environmental factors. The efficacy and quantity of these phytochemicals relies upon numerous factors including the extraction method, solvent polarity and the habitat features in which the plant is growing. In this study we emphasized on phytochemical analysis and antioxidant activity of Bistorta amplexicaulis, an important medicinal plant species from Kashmir Himalaya. We evaluated antioxidant activity using different assays from all the selected sites to enumerate the impact of habitat. The sites were selected based on varying habitat features and altitude. Our results revealed that Ethyl acetate is the potent solvent for the extraction of phytochemicals. Below ground parts exhibited better scavenging activity than the above ground parts. Amongst the sites, we found the maximum antioxidant potential at Site I. A positive correlation was found between antioxidant activity and altitude while soil attributes (OC, OM, N, P, and K) and most of the morphological traits showed a negative correlation. Overall, our study identified the elite populations that could be utilized for mass propagation and harness the ultimate antioxidant potential of B. amplexicaulis.

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.

Association of IFN-gamma and IL-10 gene variants with the risk of extrapulmonary tuberculosis.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is a chronic infectious disease. Interferon-gamma (IFN-γ) is an important cytokine imparting resistance to mycobacterial diseases. It is believed that IFN-γ and Interleukin-10 (IL-10) play divergent roles in the host immune system against MTB infection. IL-10 is an important inhibitory cytokine and helps balancing the inflammatory and immune responses. IL-10 is involved in down regulation of Th1 cytokines, MHC class II antigen and co-stimulatory molecular expression on macrophages, while IFN-γ results in macrophage activation allowing them to exert the microbicidal role. The objectives were to find out the association of IL-10 (-1082 A/G) and IFN-γ (+874 A/T) single nucleotide polymorphisms (SNPs) with extrapulmonary tuberculosis in ethnic Kashmiri population. A total of 100 extrapulmonary tuberculosis cases and 102 healthy controls were analyzed for IL-10 (-1082 A/G) and IFN- γ (+874 A/T) SNPs using Allele-Specific PCR. We found a significant association of IFN-γ + 874 'TT' genotype with extrapulmonary tuberculosis (p = 0.006) and in case of IL-10 (-1082 A/G) we found a significant association with extrapulmonary tuberculosis under recessive model (GG vs GA + AA) (p = 0.03) in Kashmiri population. IL-10 (-1082 A/G) and IFN-γ (+874 A/T) have a significant association with extrapulmonary tuberculosis in ethnic Kashmiri population.

Role of genetic variants of Vitamin D receptor, Toll-like receptor 2 and Toll-like receptor 4 in extrapulmonary tuberculosis.

BACKGROUND: Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB). Vitamin D deficiency and vitamin D receptor (VDR) gene abnormalities confer susceptibility to tuberculosis. Toll-like receptors (TLRs), such as TLR-2, are also important mediators of inflammatory response against Mycobacterium tuberculosis. We evaluated VDR, TLR-2 and TLR-4 gene polymorphisms in patients with extrapulmonary tuberculosis (EPTB). OBJECTIVES: To find out a possible association of Vitamin D receptor (VDR) (rs731236), TLR-2 (196-174 Ins > Del) and TLR-4 (Thr399Ile) gene polymorphisms with extrapulmonary tuberculosis in ethnic Kashmiri population. METHODS: A total of 100 extrapulmunary tuberculosis cases and 102 healthy controls were analyzed for Vitamin D receptor (VDR) (rs731236), TLR-2 (196-174 ins > del) and TLR-4 (Thr399Ile) gene polymorphisms using PCR-RFLP and Allele-Specific PCR methods. RESULTS: We found increased frequency of TLR-4 Thr/Ile heterozygous genotype in cases as compared with healthy controls (22% vs 5.8%). Thus acting as a risk factor for extrapulmonary tuberculosis, as was elucidated from statistical analysis [OR, 4.5; 95% CI (1.74-11.68); P < 0.001]. In case of TLR-2 (196-174 ins > del) we observed significant differences in the homozygous variant (Del/Del) genotype of cases and controls (28% in cases & 2.94% in controls). Thus, TLR-2 (Del/Del) genotype acts as a strong risk factor for extrapulmonary tuberculosis predisposition [OR, 12.2; 95% CI (3.5-42.69); P < 0.001]. We did not find any significant differences in the genotypic distribution of (VDR) (rs731236) T > C SNP between cases and controls (P > 0.05). CONCLUSION: TLR-4 (Thr/Ile) and TLR-2 (Del/Del) act as significant risk factors for extrapulmonary tuberculosis predisposition in ethnic Kashmiri population.

Disseminated intravascular coagulation presenting as symmetrical peripheral gangrene: a case report.

INTRODUCTION: Plasmodium vivax was traditionally thought to be benign; however, nowadays it presents with a myriad of systemic complications like cerebral malaria, acute respiratory distress syndrome, acute kidney injury, acute pancreatitis, hepatic dysfunction, and disseminated intravascular coagulation, which were earlier attributed only to Plasmodium falciparum malaria. Here we report a case of a middle-aged man who presented with disseminated intravascular coagulation manifesting as symmetrical peripheral gangrene. What makes this case more interesting is that the malaria isolated was Plasmodium vivax instead of Plasmodium falciparum. Such findings were previously reported, but this is the first case where the patient was managed conservatively with antimalarial drugs without the need for amputation, which focuses on the very important role of early diagnosis and timely management. CASE PRESENTATION: A 44-year-old Indian man from north India presented with history of fever of 2 days' duration with severely painful cold extremities. No pulse could be recorded on examination. A diagnosis of symmetrical peripheral gangrene was made. During the etiological evaluation, Plasmodium vivax malaria was found leading to disseminated intravascular coagulation causing this complication. He was started on artesunate and lumefantrine combination therapy and he recovered completely without the requirement of amputation. CONCLUSION: This case highlights the non-benign nature of Plasmodium vivax and its emerging complications. Also it correlates symmetrical peripheral gangrene with Plasmodium vivax malaria. It also emphasizes the importance of timely diagnosis and intervention to reduce mortality and morbidity.

Evaluation of iron deficiency anaemia for gastrointestinal causes in patients without GI symptoms in high prevalent GI malignancy zones.

BACKGROUND AND STUDY AIMS: Gastric cancer is highly prevalent in Kashmir, as are lower gastrointestinal (LGI) malignancies. Colonic cancer, gastric cancer, and coeliac disease are the most important gastrointestinal (GI) causes of iron deficiency anaemia (IDA) worldwide. Approximately 9% of patients with IDA present with a suspicious lesion in the GI tract upon examination. However, the absence of GI symptoms and a possible lesion accounting for blood loss in IDA have not been studied in this zone with a high prevalence of GI malignancy. We aimed to examine IDA patients without GI symptoms to determine the most plausible cause of their blood loss. PATIENTS AND METHODS: A total of 100 patients with IDA and 250 control subjects without IDA and referred for gastrointestinal endoscopy were enrolled in a cross-sectional, comparative study. Patients presenting with a significant lesion proportionate to their anaemia in the upper GI tract were not examined further, if no further strong indications were present. RESULTS: Twenty-nine patients (29%) were found to have malignancy: 13 with gastric cancer and 16 with colonic malignancies. Other apparent causes of GI blood loss included peptic ulcer disease in 10 (10%) patients, haemorrhoids in 22 (25%), polyps in eight (three in the upper GI tract and five in the LGI tract), gastric erosions in eight (8%), and angiodysplasia, diverticulitis, and trichuriasis in two (2%) each. CONCLUSION: In light of the high incidence of GI malignancies in this patient group, a low threshold for GI screening as well as mass screening for IDA is needed.

Wood specific gravity variation among five important hardwood species of Kashmir Himalaya.

Wood Specific Gravity (SG) is a measure of the amount of structural material a tree species allocates to support and strength. In the present study, specific gravity varied among the five different woods at three different sites from 0.40 in Populus nigra at site III (Shopian) to 0.80 in Parrotiopsis jacquemontiana at site II (Surasyar). Among the three different sites, specific gravity varied from 0.73 to 0.80 in Parroptiosis jacquemontiana; in Robinia pseudoacacia it varied from 0.71 to 0.79; in Salix alba, it varied from 0.42 to 0.48; In Populus nigra it varied from 0.40 to 0.48 and in Juglans regia it varied from 0.59 to 0.66. On the basis of the specific gravity variation patterns these woods were categorized as light (Salix alba, Populus nigra) moderately heavy (Juglans regia) and moderately heavy to heavy (Robinia pseudoacacia, Parrotiopsis jacquemontiana) which predicts their properties like strength, dimensional stability with moisture content change, ability to retain paint, fiber yield per unit volume, suitability for making particleboard and related wood composite materials and suitability as a raw material for making paper.

Effect of Ajuga bracteosa on systemic T-cell immunity in Balb/C mice: dual Th1/Th2 immunostimulatory effects.

Ajuga bracteosa (AB) has been widely used in folk medicine in Asian countries against gout, hepatitis, pneumonia, rheumatism, and various neuro inflammatory disorders. The aim of this study was to investigate the possible immunoregulatory effects of the ethanolic extract of Ajuga bracteosa (ABEE) on systemic Th1/Th2 immunity in SRBC immunized Balb/C mice. Animals were orally administered with graded doses of ABEE from 6.25 mg/kg to 100 mg/kg. Post sub-cutaneous immunization with SRBCs and circulating antibody titers, DTH responses and splenocyte proliferation was monitored as markers of Th2 and Th1 responses. Cyclophosphamide and levamisole were used as controls. Lymphocyte immunophenotying (CD4/CD8 cell counts) and intracellular Th1/Th2 cytokine concentrations were determined using flow cytometry. Treatment with ABEE demonstrated significant biphasic immunostimulation of effector T-helper immunity. ABEE at 50 mg/kg dose resulted in maximal increase in antibody titers, DTH responses and CD4+/CD8+ T-cell percentages indicating maximal activation and proliferation of T and B lymphocytes at this dose. ABEE, at the same dose, also showed maximal up regulation of LPS and CON A stimulated splenocyte proliferation and also maximal up-regulation of both Th1 (IL-2, IFN-γ) and Th2 (IL-4) cytokines which suggest its mixed Th1/Th2 immunostimulatory activity. Comparatively at higher doses (100 mg/kg), significant down regulation of all these effector T-helper (Th) immune responses was observed. The study therefore suggests mixed biphasic immunostimulatory Th1/Th2 activity of ABEE that could support its immunoadjuvant potential.

Induction of apoptosis in human pancreatic MiaPaCa-2 cells through the loss of mitochondrial membrane potential (ΔΨm) by Gentiana kurroo root extract and LC-ESI-MS analysis of its principal constituents.

The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo for antioxidant and antiproliferative activities as well as to study the effect of the extract on the induction of apoptosis in human pancreatic cancer cell line (MiaPaCa-2). The extract exerted significant antioxidant activity as verified by DPPH, hydroxyl radical, lipid peroxidation and protective oxidative DNA damage assays. The results were comparable to standard antioxidants like α-tocopherol, catechin and BHT used in such experiments. Antioxidant potential of G. kurroo may be attributed to the presence of high phenolic and flavonoid content (73±1.02 and 46±2.05 mg/g extract respectively). The anti-proliferative property of Gentiana kurroo root extract was determined by sulphorhodamine B (SRB) assay against Human colon cancer cell line (HCT-116), Lung carcinoma cell line (A-549), Pancreatic cancer cell line (MiaPaCa-2), Lung cancer cell line (HOP-62) and acute monocytic leukaemia cell line (THP-1). G. kurroo root extract inhibited cancer cell growth depending upon the cell line used and in a dose dependent manner. The extract induced potent apoptotic effects in MiaPaCa-2 cells. The population of apoptotic cells increased from 11.4% in case of control to 49.6% at 100 µg/ml of G. kurroo root extract. The extract also induced a remarkable decrease in mitochondrial membrane potential (ΔΨm) leading to apoptosis of cancer cells used. The main chemical constituents identified by the liquid chromatography-tandem mass spectrometry (LC-ESI-MSMS) were found to be iridoid glucosides (iridoids and secoiridoids), xanthones and flavonoids. Iridoid glucosides are the bitter principles of Gentiana species. Loganic acid, Sweroside, Swertiamarin, Gentiopicroside, Gentisin, Isogentisin, Gentioside, Norswertianolin, Swertianolin, 4″-O-ß-D-glucosyl-6'-O-(4-O-ß-D-glucosylcaffeoyl)-linearoside and Swertisin were the principal compounds present in the methanol root extract of G. kurroo.

Promoter methylation status of DNA repair gene (hMLH1) in gastric carcinoma patients of the Kashmir valley.

Cancer is a multi-factorial disease and variation in genetic susceptibility, due to inherited differences in the capacity to repair mismatches in the genome, is an important factor in the development of gastric cancer (GC), for example. Epigenetic changes, including aberrant methylation of 5/CpG islands in the promoter regions of mismatch repair (MMR) genes like hMLH1, have been implicated in the development of various types of GC. In the present study we evaluated the role of hMLH1 promoter hypermethylation in Kashmiri GC patients and controls, and assessed correlations with various dietary and lifestyle factors. The study included 70 GC patients (56 males and 14 females; age (mean ± S.D) 50 ± 11.4 years). Distinction between methylated and unmethylated was achieved with MS-PCR and DNA band patterns. The Chi-square test was applied to assess the risk due to promoter hypermethylation. We found a strikingly high frequency of promoter hypermethylation in GC cases than in normal samples (72.9% (51/70) in GC cases vs 20% (14/70) in normal samples (p=0.0001). We also observed a statistically significant association between methylated hMLH1 gene promoter and smoking, consumption of sundried vegetables and hot salted tea with the risk of GC. This study revealed that hMLH1 hypermethylation is strongly associated with GC and suggested roles for epigenetic changes in stomach cancer causation in the Kashmir valley.

Chemical composition, antioxidant and antibacterial activities of the leaf essential oil of Juglans regia L. and its constituents.

The essential oil from the leaves of Juglans regia L. (Juglandaceae) growing wild in Kashmir (India) was obtained by hydrodistillation and analysed by a combination of capillary GC-FID and GC-MS. A total of 38 compounds, representing 92.7% of the oil, were identified and the major components were found to be α-pinene (15.1%), ß-pinene (30.5%), ß-caryophyllene (15.5%) germacrene D (14.4%) and limonene (3.6%). The essential oil and the main individual constituents were screened for antibacterial activity and the essential oil evaluated for antioxidant activity. Antibacterial activity was evaluated using the disc diffusion and microdilution methods against a group of clinically significant Gram-positive (Staphylococcus epidermidis MTCC-435, Bacillus subtilis MTCC-441, Staphylococcus aureus) and Gram-negative bacteria (Proteus vulgaris MTCC-321, Pseudomonas aeruginosa MTCC-1688, Salmonella typhi, Shigella dyssenteriae, Klebsiella pneumonia and Escherichia coli). The essential oil and its major components exhibited broad spectrum inhibition against all the bacterial strains with Gram-positive being more susceptible to the oil than Gram-negative bacteria. Antioxidant activity of the oil was evaluated by the scavenging effect on DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radicals. In general, the essential oil exhibited high antioxidant activity which was comparable to the reference standards at the same dose (ascorbic acid and butylated hydroxyl toluene, BHT) with IC(50) values of 34.5 and 56.4µg/ml calculated by DPPH and hydroxyl radical scavenging assays respectively.

Nutritional values and antioxidant potential of some edible mushrooms of Kashmir valley.

Mushrooms are considered rich in proteins, carbohydrates and other nutrients. The present study was carried out to evaluate some edible mushrooms of Kashmir valley for their protein, carbohydrate and lipid contents. The highest protein content was found in Boletus edulis (2.20g) followed by Agaricus bisporus (1.80g), Pleurotus ostreatus (1.68g), Morchella esculenta (1.62g) and Pleurotus sajor caju (1.6g). Carbohydrate content also showed variation in all the five tested edible mushroom species, the highest carbohydrate content observed in Boletus edulis (6.0g) followed by Agaricus bisporus (4.85g), Pleurotus ostreatus (4.30g), Morchella esculenta (4.25g) and Pleurotus sajor caju (3.35g) respectively. Similar results were observed for lipid content. The present study was also investigated for the antioxidant potential of aqueous extract of mushroom species by the methods of DPPH radical scavenging activity, hydroxyl radical scavenging activity and superoxide radical scavenging activity. All these in vitro antioxidant activities were concentration dependent, which were compared with standard antioxidant Catechin.