Metabolomics-based pharmaceutical evaluation of different parts of Swertia chirayita (Roxb.) Buch.-Ham. ex C.B. Clarke from the western Himalayas.

Swertia species are common ingredients in numerous herbal remedies. It is also used to treat a wide range of illnesses and possess diverse therapeutic activities. The aim of the study is to elucidate the comprehensive metabolomics profile of Swertia chirayita and the role of various extraction methods in the phytochemical compositions of the extracts of S. chirayita, and their antioxidant and enzyme inhibitory activities. Extraction of the stems, leaves, and flowering tops of S. chirayita was performed by maceration, infusion, and soxhlation using methanol and water as solvent. Extracts were subjected to phytochemical profiling by a liquid-chromatographic system. Antioxidant and enzyme inhibitory activity was carried out. The metabolomics profiling showed that a diverse range of specialized metabolites were present in the stems and leaves & flowering tops of the plant. All the extracts showed substantial antioxidant and enzyme inhibitory activities further confirmed by molecular docking studies. This study appraised the use of S. chirayita aerial parts as a potential antioxidant and its therapeutic application in various chronic illnesses including Alzheimer's disease, diabetes, and other skin-related disorders.

Targeting Cell Signaling Pathways in Lung Cancer by Bioactive Phytocompounds.

Lung cancer is a heterogeneous group of malignancies with high incidence worldwide. It is the most frequently occurring cancer in men and the second most common in women. Due to its frequent diagnosis and variable response to treatment, lung cancer was reported as the top cause of cancer-related deaths worldwide in 2020. Many aberrant signaling cascades are implicated in the pathogenesis of lung cancer, including those involved in apoptosis (B cell lymphoma protein, Bcl-2-associated X protein, first apoptosis signal ligand), growth inhibition (tumor suppressor protein or gene and serine/threonine kinase 11), and growth promotion (epidermal growth factor receptor/proto-oncogenes/phosphatidylinositol-3 kinase). Accordingly, these pathways and their signaling molecules have become promising targets for chemopreventive and chemotherapeutic agents. Recent research provides compelling evidence for the use of plant-based compounds, known collectively as phytochemicals, as anticancer agents. This review discusses major contributing signaling pathways involved in the pathophysiology of lung cancer, as well as currently available treatments and prospective drug candidates. The anticancer potential of naturally occurring bioactive compounds in the context of lung cancer is also discussed, with critical analysis of their mechanistic actions presented by preclinical and clinical studies.

Himalayan Citrus jambhiri juice reduced renal crystallization in nephrolithiasis by possible inhibition of glycolate oxidase and matrix metalloproteinases.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrus fruits are a very rich source of electrolytes and citric acid. They have been used traditionally for treating urinary ailments and renal stones. Citrus jambhiri is indigenously used as a diuretic. AIM OF THE STUDY: Present study aimed at establishing the antiurolithiatic potential of the juice of Citrus jambhiri fruits along with the elucidation of the mechanism involved in the urolithiasis disease defying activity. METHODS: The antiurolithiatic activity was established by means of nucleation, growth and aggregation assay in the in vitro settings and by means of ethylene glycol mediated calcium oxalate urolithiasis in the male Wistar rats. Docking studies were performed in an attempt to determine the mechanism of the antiurolithiatic action. RESULTS: Present study revealed the role of C. jambhiri fruit juice in reducing nucleation, growth and aggregation of calcium oxalate crystals by possible reduction in the urinary supersaturation relative to calcium oxalate and raising the zeta potential of the calcium oxalate crystals. C. jambhiri fruit juice treatment in experimental rats produced significant amelioration of hypercalciuria, hyperoxaluria, hyperphosphaturia, hyperproteinuria, hyperuricosuria, hypocitraturia and hypomagnesiuria and ion activity product of calcium oxalate. It exhibited nephroprotection against calcium oxalate crystals induced renal tubular dilation and renal tissue deterioration. Docking studies further revealed high binding potential of the phytoconstituents of C. jambhiri viz. narirutin, neohesperidin, hesperidin, rutin and citric acid with glycolate oxidase and matrix metalloproteinase-9. CONCLUSION: C. jambhiri fruit juice possesses excellent antiurolithiatic activity. The study reveals antiurolithiatic mechanism that involves restoration of equilibrium between the promoters and inhibitors of stone formation; and inhibition of matrix metalloproteinases and glycolate oxidase.

Himalayan Ficus palmata L. Fruit Extract Showed In Vivo Central and Peripheral Analgesic Activity Involving COX-2 and Mu Opioid Receptors.

Analgesic drugs like morphine and non-steroidal anti-inflammatory drugs exhibit several harmful effects. Here, we show for the first time the analgesic activity of Ficus palmata L. fruit extract (FPFE) on different analgesic rat models along with the in silico studies of some of the main phytochemicals of this plant. We performed in vivo pain models, along with in silico docking studies against the active site of COX-2 protein and mu-opioid receptors. A significant (p < 0.05) analgesic effect of FPFE was observed, and it was found that rutin has good pose and score as compared to diclofenac and morphinan antagonist (X-ligand), and psoralen has binding affinity almost equal to diclofenac, but a lower binding affinity as compared to rutin. The results proved that F. palmata fruits have the potential to ameliorate painful conditions.

Targeting the crosstalk between canonical Wnt/ß-catenin and inflammatory signaling cascades: A novel strategy for cancer prevention and therapy.

Emerging scientific evidence indicates that inflammation is a critical component of tumor promotion and progression. Most cancers originate from sites of chronic irritation, infections and inflammation, underscoring that the tumor microenvironment is largely orchestrated by inflammatory cells and pro-inflammatory molecules. These inflammatory components are intimately involved in neoplastic processes which foster proliferation, survival, invasion, and migration, making inflammation the primary target for cancer prevention and treatment. The influence of inflammation and the immune system on the progression and development of cancer has recently gained immense interest. The Wnt/ß-catenin signaling pathway, an evolutionarily conserved signaling strategy, has a critical role in regulating tissue development. It has been implicated as a major player in cancer development and progression with its regulatory role on inflammatory cascades. Many naturally-occurring and small synthetic molecules endowed with inherent anti-inflammatory properties inhibit this aberrant signaling pathway, making them a promising class of compounds in the fight against inflammatory cancers. This article analyzes available scientific evidence and suggests a crosslink between Wnt/ß-catenin signaling and inflammatory pathways in inflammatory cancers, especially breast, gastrointestinal, endometrial, and ovarian cancer. We also highlight emerging experimental findings that numerous anti-inflammatory synthetic and natural compounds target the crosslink between Wnt/ß-catenin pathway and inflammatory cascades to achieve cancer prevention and intervention. Current challenges, limitations, and future directions of research are also discussed.

Role of Nitric Oxide in Neurodegeneration: Function, Regulation, and Inhibition.

Reactive nitrogen species (RNS) and reactive oxygen species (ROS), collectively known as reactive oxygen and nitrogen species (RONS), are the products of normal cellular metabolism and interact with several vital biomolecules including nucleic acid, proteins, and membrane lipids and alter their function in an irreversible manner which can lead to cell death. There is an imperative role for oxidative stress in the pathogenesis of cognitive impairments and the development and progression of neural injury. Elevated production of higher amounts of nitric oxide (NO) takes place in numerous pathological conditions, such as neurodegenerative diseases, inflammation, and ischemia, which occur concurrently with elevated nitrosative/oxidative stress. The enzyme nitric oxide synthase (NOS) is responsible for the generation of NO in different cells by conversion of Larginine (Arg) to L-citrulline. Therefore, the NO signaling pathway represents a viable therapeutic target. Naturally occurring polyphenols targeting the NO signaling pathway can be of major importance in the field of neurodegeneration and related complications. Here, we comprehensively review the importance of NO and its production in the human body and afterwards highlight the importance of various natural products along with their mechanisms against various neurodegenerative diseases involving their effect on NO production.

Anticalcifying effect of Daucus carota in experimental urolithiasis in Wistar rats.

BACKGROUND: Urolithiasis is a burgeoning disease that results from pathological biomineralization. Daucus carota L. is a widely consumed food crop with reported nephroprotective and diuretic activity. Its potential for Ashmari bhedan (destruction of stone/calculi) or treatment of urinary calculi has been explored traditionally. However, no scientific evidence is available to prove its antiurolithiatic efficacy. Moreover, establishing the antiurolithiatic effects of D. carota, an extensively consumed commodity with numerous health benefits, would provide a beneficial dietary measure for the prevention and cure of urolithiasis. OBJECTIVE: The study aimed at investigating in vivo antiurolithiatic potential of hydroethanolic extract of D. carota roots against calcium oxalate urolithiasis. MATERIALS AND METHODS: Ethylene glycol and ammonium chloride induced hyperoxaluria model of urolithiasis in male Wistar rats was used for the study. Urine and serum parameters and, kidney histopathology was used to determine the antilithic efficacy of D. carota root extract. RESULTS: D. carota extract significantly ameliorated abnormal urinary levels of calcium, oxalate, phosphate, magnesium, citrate, protein and uric acid in lithogenic rats. Serum BUN, creatinine and uric acid levels; and calcium, phosphate and oxalate deposition in kidney tissue were also rendered normal following D. carota treatment. D. carota extract also prevented oxidative stress mediated renal tissue degeneration both prophylactically and curatively. CONCLUSION: This study suggests antiurolithiatic effect of D. carota roots, which can be attributed to its anticrystallization property, ability to ameliorate urine and serum biochemistry and renal cellularity.

Targeting BDNF signaling by natural products: Novel synaptic repair therapeutics for neurodegeneration and behavior disorders.

Neurodegenerative disorders like Alzheimer's disease, Huntington's disease, Parkinson's disease, spinocerebellar ataxias, amyotrophic lateral sclerosis, frontotemporal dementia to prion diseases, Friedreich's ataxia, hereditary spastic paraplegia and optic atrophy type 1, and behavior disorders like neuropsychiatric, hyperactivity and autism spectrum disorders are closely associated with neurobiological deficits. Brain derived neurotrophic factor (BDNF) is an extensively studied neurotrophin. BDNF is essential for neuronal genesis, differentiation, survival, growth, plasticity, synaptic viability and transmission. BDNF has emerged as a promising target for regulating synaptic activity and plasticity. An overview of effects and mechanisms of the natural products targeting BDNF is described. This review is an attempt to enumerate the effects of various natural products on BDNF as a novel therapeutic approach for neurodegenerative and neuropsychiatric disorders.

Down syndrome: Neurobiological alterations and therapeutic targets.

Down syndrome (DS) is a genetic disease that occurs due to an aneuploidy of human chromosome 21. Trisomy of chromosome 21 is a primary genetic cause of developmental abnormalities leading to cognitive and learning deficits. Impairments in GABAergic transmission, noradrenergic neuronal loss, anomalous glutamatergic transmission and N-methyl-d-aspartate receptor signalling, mitochondrial dysfunction, increased oxidative stress and inflammation, differentially expressed microRNAs, increased expression of crucial chromosome 21 genes, and DNA hyper-methylation and hyperactive homocysteine trans-sulfuration pathway, are common incongruities that have been reported in DS and might contribute to cognitive impairment and intellectual disability. This review provides an update on metabolic and neurobiological alterations in DS. It also provides an overview of the currently available pharmacological therapies that may influence and/or reverse these alterations in DS.