Ethanol extract of Ziziphus nummularia ameliorates formaldehyde-induced arthritis in rats by regulating oxidative stress biomarkers and haematological profile.

BACKGROUND: Rheumatoid arthritis is an autoimmune inflammatory disorder that mainly affects bone and cartilage architecture. The continuous use of NSAIDs and DMARDs is associated with severe toxic effects. Therefore, the current study was designed to scrutinize herb-based therapy for the treatment of RA. AIM: To evaluate the anti-arthritic activity of ethanol extract of Ziziphus nummularia using formaldehyde-induced arthritic model in rats and elucidate the possible mechanism for anti-arthritic activity. MATERIALS AND METHODS: Anti-arthritic activity of ETZN was studied at three oral doses, i.e., 200, 400, and 600 mg/kg. Selected doses were studied using various clinical parameters viz. paw volume, inflammatory index, motility test, stair test, anti-nociceptive efficacy, walking track analysis, and motor activity) from day 1 to day 10. On the last day, the animals were killed for the evaluation of hematological parameters, oxidative stress biomarkers, and histological and radiographic studies of the hind paw. RESULTS: Treatment with ETZN 400 mg/kg and 600 mg/kg markedly elicited a significant reduction in paw volume, inflammatory index, and nociceptive action compared to diseased animals. Furthermore, the anti-inflammatory activity was confirmed by increased latency of pain threshold in thermal and mechanical algesia models. The anti-arthritic activity is mainly attributed to a reduction in oxidative stress biomarkers as well as restoration of haematological profile in treated animals when compared to diseased animals. Lastly, the anti-arthritic potential was confirmed by histological and radiological analysis which revealed a marked reduction in inflammatory cells and bone destruction as compared to diseased animals. CONCLUSION: The study revealed that ETZN exhibits significant anti-arthritic activity via modulation of oxidative stress biomarkers, restoration of hematological profile, and reduction in bone erosion.

Comparison of neuraxial acoustic target window of the spine among rider sitting, cross leg, hamstring stretch, and classical sitting position: An observational study.

Background and Aims: To compare ultra-sonographic dimensions of acoustic target window of the spine in the participants at four different sitting positions namely cross leg sitting (CLP), hamstring stretch (HSP), classical sitting (CSP) and riders sitting position (RSP). The primary objective of this study was to measure the neuraxial acoustic target window (defined as interlaminar distance between L3-L4 lamina). The secondary objective was to compare ultra-sonographic measurements of the depth of ligamentum flavum from the skin, and to compare the diameter of intrathecal space and comfort score in the four different sitting positions. Material and Methods: This study is a prospective observational study. Eighty participants were included and positioned in four different sitting positions to perform an ultra-sonographic scan and measure various parameters of the acoustic neuraxial window. The interlaminar distance, the distance of skin from the ligamentum flavum, and the diameter of the spinal canal or intrathecal space was measured in the L3-L4 intervertebral space in different positions. Results: The mean value of interlaminar distance among four sitting positions was ranging from 1.40 cm to 1.44 cm (P value 0.725.) The distance of ligamentum flavum from skin and diameter of intrathecal space was also comparable in all the groups. The comfort score in CSP was significantly better when compared to other groups with a median score of 4 (P value < 0.001). Conclusions: There is no statistically significant difference in interlaminar distance in various sitting positions. All four positions are equally effective and can be used as an alternative to spinal/epidural intervention, but the CSP came out to be the most comfortable and more emphasis should be given to the comfort as it increases the chance of success rate of the procedure.

Pathogenesis and management of traumatic brain injury (TBI): role of neuroinflammation and anti-inflammatory drugs.

Traumatic brain injury (TBI) is an important global health concern that represents a leading cause of death and disability. It occurs due to direct impact or hit on the head caused by factors such as motor vehicles, crushes, and assaults. During the past decade, an abundance of new evidence highlighted the importance of inflammation in the secondary damage response that contributes to neurodegenerative and neurological deficits after TBI. It results in disruption of the blood-brain barrier (BBB) and initiates the release of macrophages, neutrophils, and lymphocytes at the injury site. A growing number of researchers have discovered various signalling pathways associated with the initiation and progression of inflammation. Targeting different signalling pathways (NF-κB, JAK/STAT, MAPKs, PI3K/Akt/mTOR, GSK-3, Nrf2, RhoGTPase, TGF-ß1, and NLRP3) helps in the development of novel anti-inflammatory drugs in the management of TBI. Several synthetic and herbal drugs with both anti-inflammatory and neuroprotective potential showed effective results. This review summarizes different signalling pathways, associated pathologies, inflammatory mediators, pharmacological potential, current status, and challenges with anti-inflammatory drugs.

Mechanistic Insights into the Pharmacological Significance of Silymarin.

Medicinal plants are considered the reservoir of diverse therapeutic agents and have been traditionally employed worldwide to heal various ailments for several decades. Silymarin is a plant-derived mixture of polyphenolic flavonoids originating from the fruits and akenes of Silybum marianum and contains three flavonolignans, silibinins (silybins), silychristin and silydianin, along with taxifolin. Silybins are the major constituents in silymarin with almost 70-80% abundance and are accountable for most of the observed therapeutic activity. Silymarin has also been acknowledged from the ancient period and is utilized in European and Asian systems of traditional medicine for treating various liver disorders. The contemporary literature reveals that silymarin is employed significantly as a neuroprotective, hepatoprotective, cardioprotective, antioxidant, anti-cancer, anti-diabetic, anti-viral, anti-hypertensive, immunomodulator, anti-inflammatory, photoprotective and detoxification agent by targeting various cellular and molecular pathways, including MAPK, mTOR, ß-catenin and Akt, different receptors and growth factors, as well as inhibiting numerous enzymes and the gene expression of several apoptotic proteins and inflammatory cytokines. Therefore, the current review aims to recapitulate and update the existing knowledge regarding the pharmacological potential of silymarin as evidenced by vast cellular, animal, and clinical studies, with a particular emphasis on its mechanisms of action.

Increasing role of abstinence and infecundity in non-use of contraceptive methods in India.

This paper assesses the reasons for non-use of contraceptive methods, and the possible complexity of reported data on women in India. The study used recent data from two successive rounds of the National Family Health Survey (NFHS) (2005-06: N=37,296; 2015-16: N=247,024), which surveyed currently married women aged 15-49 years. The reporting on non-use of contraceptives and the changing pattern of the reasons for non-use were analysed, classified into fertility and other cited reasons. The self-reported reasons for non-use of contraception were verified with other related information captured in the survey. Bivariate and logistic regression analyses were conducted. Sexual abstinence (not having sex: 10%; infrequent sex: 3%) and infecundity (menopausal/hysterectomy: 12%; subfecund/infecund: 10%) were the most commonly reported reasons for non-use of contraceptive methods in 2015-16, followed by refusal to use (10%). The proportion of non-users who wanted to have a child soon (25% to 21%), were pregnant (16% to 13%), in postpartum amenorrhoea (68% to 40%) and who had method-related reasons (10% to 6%) declined over time (from 2005-06 to 2015-16, respectively). A higher proportion of less-educated women reported abstinence (6%) and menopause/hysterectomy (19%) than educated women. Abstinence was more commonly reported in states with low prevalence of modern contraceptive use. The findings suggest that the increasing trend of abstinence and infecundity among non-users of contraception may be a concern for future research and reproductive health programmes, as it questions both the quality of data and sexual health of married couples.

Infections, genetic and environmental factors in pathogenesis of autoimmune thyroid diseases.

In Autoimmune disease a combination of infection, genetic and environmental factors causes an autoimmune response to the thyroid gland (characterized by lymphocytic infiltrations), thyroid stimulating hormone receptor (TSHR) and different thyroid antigens. Graves' and Hashimoto disease are autoimmune disorders with genetic predisposition. CD40 that stimulates the proliferation and differentiation of lymphocytes is an essential immunomodulatory component for follicular cells in the thyroid and the cell that present the antigen. CD40, PTPN22 and thyroid-specific genes are immunomodulating genes for the TSH receptor and thyroglobulin. CD40 used to be associated with Graves's disease as positional candidate on the basis of Graves' disease linkage study connecting with 20q11 genome chromosomal region. The PTPN22 gene gives rise to a substantial risk of specific autoimmune phenotypes and frequent disease mechanisms. Infections have been implicated in the pathogenesis of AITD including Coxsackie virus, Yersinia enterocolitica, Borrelia burgdorferi, Helicobacter pylori and retroviruses (HTLV-1, HFV, HIV and SV40). Infectious hepatitis C agents are the strongest proof supporting an affiliation with AITD. The essential environmental triggers of AITD are iodine, drugs, infection, smoking and perhaps stress. Autoimmune disease provide important facts on genetic mechanisms that influence the prognosis and treatment of the disease and by recent molecular techniques through gene expression study by quantitative Real Time-PCR and microarray, we can identify novel genes which are responsible for Graves' and Hashimoto disease.

Interlink between cholesterol & cell cycle in prostate carcinoma.

Background & objectives: Earlier reports have shown hypocholesterolaemia in cancer patients and high number of lipid rafts in cancer cells. The primary objective of this study was to compare the intracellular cholesterol turnover in non-cancerous (benign) prostatic hyperplasia (BPH) and carcinoma prostate (CAP) with normal prostate cells obtained from patients undergoing radical cystectomy for carcinoma bladder (sham control). Methods: ELISA-based estimation of prostate-specific antigen (PSA), evaluation of expression of low-density lipoprotein receptor (LDLR), peripheral-type benzodiazepine receptor (PBR) and cyclin E, immunohistochemistry and confocal microscopy, measurement of integrated optical density of the diaminobenzidine (DAB)-stained immunohistograms, isolation of nucleus and cell cytoplasm from prostate tissue by ultracentrifugation followed by estimation of cholesterol spectrophotometrically in isolated nuclear and cytoplasmic fractions were performed. Results: Seventy five individuals, 25 for each group (BPH n=25; CAP n=25 and sham control n=25), were included in the study. Cholesterol was increased in the cytoplasm and nucleus of the prostate cancer cells along with elevated expression of LDLR. Increased cholesterol concentration in the cell nucleus was found comparable with the increased expression of cholesterol transporter viz. PBR in the prostate tumour tissues as compared to its expression in normal prostate cells obtained from individuals undergoing radical cystectomy for carcinoma bladder. Cell cycle protein cyclin E was also highly expressed in cancer tissues. Interpretation & conclusions: The present findings along with increased expression of cell cycle protein cyclin E in the cell nucleus of the tumour tissue suggested the possibility of an intriguing role of cholesterol in the mechanism of cell cycle process of prostate cell proliferation.

A Cascade "Prins-Pinacol-Type Rearrangement and C4-OBn Participation" on Carbohydrate Substrates: Synthesis of Bridged Tricyclic Ketals, Annulated Sugars and C2-Branched Heptoses.

A "Prins pinacol type rearrangement followed by C4-OBn participation" in a cascade manner has been observed while probing the fate of carbocation in some carbohydrate derived homoallylic alcohols in the Prins reaction. This has led to an easy access to tetrahydrofuran-fused bridged bicyclic ketals (or tetrahydrofuran-fused 1,6-anhydro-heptopyranose frameworks) which are further converted into some annulated sugars and C2-branched heptoses.

Acorus calamus Linn.: A novel neuroprotective approach for traumatic brain injury in Drosophila melanogaster.

BACKGROUND: Traumatic brain injury (TBI) causes substantial mortality and morbidity globally. Current treatments only alleviate symptoms and do not halt secondary injury progression. OBJECTIVES: Evaluate the neuroprotective potential of Acorus calamus Linn. (AC) in a Drosophila melanogaster model of high-impact TBI. METHODS: Fruit flies (Drosophila melanogaster) of the Oregon R + strain were administered hydroalcoholic extracts of Acorus calamus Linn. (HAEAC) at concentrations of 25 and 50 µg/mL, 24 h and continuously for 72 h, respectively, following TBI induction. Mortality rate, locomotor function, neurotransmitter levels, and oxidative stress markers were assessed at 24 and 72 h post-injury as outcomemeasures. RESULTS: AC significantly reduced post-TBI mortality and improved locomotor function in a dose-dependent manner. Additionally, AC increased acetylcholinesterase, gamma-aminobutyric acid, serotonin, and dopamine levels while reducing glutamate. It also boosted antioxidant activity (superoxide dismutase, glutathione, and catalase) and lowered markers of oxidative damage (malondialdehyde, nitrite). CONCLUSIONS: AC mitigated behavioral deficits, oxidative damage, and neurotransmitter imbalance in fruit flies after TBI. These findings indicate AC may be more effective than individual drugs for TBI therapy. Further research into its neuroprotective phytochemicals is warranted.

Pharmaceutical co-crystals: A green way to enhance drug stability and solubility for improved therapeutic efficacy.

Pharmaceutical co-crystals have gained significant attention in recent years as a promising green and sustainable method for poorly soluble drugs to improve their solubility, stability, and bioavailability. In the drug development research field, it is an extremely useful technique as it does not require a large number of synthetic steps as well a minimum amount of solvent is utilized or sometimes without solvent. This review presents a comprehensive investigation into the design, synthesis, characterization, and evaluation of pharmaceutical co-crystals. The study focuses on exploring different strategies for co-crystal formation, including co-grinding, solvent evaporation, and liquid-assisted grinding. Various characterization techniques such as SCXRD, PXRD, FTIR, and DSC were employed to confirm the formation and structural features of the co-crystals. The article also highlights the significance of understanding the intermolecular interactions within co-crystals and their influence on physicochemical properties. Furthermore, the article discusses the potential applications of pharmaceutical co-crystals in enhancing drug solubility, dissolution rate, and oral bioavailability, leading to improved therapeutic efficacy. Overall, this review provides valuable insights into the design and development of pharmaceutical co-crystals, offering a promising avenue for overcoming the difficulties brought on by poorly soluble drugs.

Antioxidative and neuroprotective potential of Acorus calamus linn. and Cordia dichotoma G. Forst. In Alzheimer's type dementia in rodent.

The goal of this research study was to see how plant extracts of Acorus calamus Linn. and Cordia dichotoma G. Forst. overcome scopolamine-induced Alzheimer's type dementia in mice by activating the cholinergic system, anti-oxidant and protection of neuronal death in the brain (hippocampus region). Scopolamine (1 mg/kg i.p.) reduced mice's routine in behavioral parameters such as Morris Water Maze (MWM), Elevated Plus Maze (EPM), and also the locomotor activity. It also decreases antioxidant levels such as Reduced glutathione (GSH) and also Superoxide dismutase (SOD) but also increases the level of Acetylcholinesterase enzyme (AChE) in brain. Assessment of various behavioral, and biochemical parameters (AChE, SOD, GSH, and Nitrite level) were compared with each group. Acorus calamus (hydro-alcoholic 1:1) 600 mg/kg p.o. and the combination (Acorus calamus 600 mg/kg p.o. + Cordia dichotoma 750 mg/kg p.o.) group showed significant results as compared to Cordia dichotoma 750 mg/kg p.o.in behavioral as well as in biochemical parameters. Histological studies showed significant neuroprotection in the Acorus calamus-treated group and the combination-treated groups. In the future, the Acorus calamus and the combination are possibly helpful in the treatment of various cognitive disorders or it may be valuable to investigate the pharmacological potential of such plant extracts during the treatment of neurodegenerative disorders.

Anti-viral Effects of Pavetta indica Methanolic Extract and Acyclovir on Behavioral and Biochemical Parameters in Streptozotocin-induced Alzheimer's Disease in Rats.

BACKGROUND: Alzheimer's disease is a neurological dysfunction of the brain caused by neurodegeneration and oxidative stress. Some viruses, such as herpes viruses, HSV-1, and HSV-2, are causative agents of Alzheimer's disease and result in ß-amyloid peptide and tau protein accumulation in the brain. Some antiviral drugs, such as valacyclovir, acyclovir, and foscarnet, reduce amyloid-beta and P-tau. Pavetta indica leaves are also reported for their antiviral properties. The current study aimed to find out the significance of using Pavetta indica methanolic extract and acyclovir against Alzheimer's disease induced by streptozotocin. METHODS: Wistar rats received acyclovir and Pavetta indica methanolic extract orally at different dose ranges (50, 150, 450 mg/kg) and (125, 250, 500 mg/kg), respectively. The standard therapy, Rivastigmine (2 mg/kg), was given orally. RESULTS: Intracerebroventricular-streptozotocin produced significant alternations in behavioral assessments, including locomotor activity test, Morris water maze test, and elevated plus maze test. Moreover, intracerebroventricular-streptozotocin ameliorated the antioxidant defense activity by decreasing levels of catalase, superoxide dismutase, and reduced glutathione while enhancing the oxidative stress markers, including malondialdehyde, and total nitrite levels. Finally, the main findings showed that intracerebroventricular-streptozotocin significantly increased the inflammatory marker, tumor necrosis factor-α, and disturbed neurotransmitter mediators, including levels of acetylcholinesterase, glutamate, and γ-amino butyric acid. CONCLUSION: In a dose-dependent manner, acyclovir and Pavetta indica methanolic extract treatments abrogated the streptozotocin-induced behavioral and neurological abnormalities in rats. The potential therapeutic effects of PIME and acyclovir administration in intracerebroventricular-streptozotocin-treated rats may be attributed to its potential antiviral, antioxidant, and anti-inflammatory effects. The current study suggests that Pavetta indica methanolic extract and acyclovir are promising therapeutic targets against Alzheimer's disease.

Targeting brain tumors with innovative nanocarriers: bridging the gap through the blood-brain barrier.

Background: Glioblastoma multiforme (GBM) is recognized as the most lethal and most highly invasive tumor. The high likelihood of treatment failure arises from the presence of the blood-brain barrier (BBB) and stem cells around GBM, which avert the entry of chemotherapeutic drugs into the tumor mass. Objective: Recently, several researchers have designed novel nanocarrier systems like liposomes, dendrimers, metallic nanoparticles, nanodiamonds, and nanorobot approaches, allowing drugs to infiltrate the BBB more efficiently, opening up innovative avenues to prevail over therapy problems and radiation therapy. Methods: Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases, for example, PubMed, Science Direct, Google Scholar, and others, using specific keyword combinations, including "glioblastoma," "brain tumor," "nanocarriers," and several others. Conclusion: This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM management. Elucidation of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

Investigating the Potential Therapeutic Mechanisms of Puerarin in Neurological Diseases.

Plants and their derived phytochemicals have a long history of treating a wide range of illnesses for several decades. They are believed to be the origin of a diverse array of medicinal compounds. One of the compounds found in kudzu root is puerarin, a isoflavone glycoside commonly used as an alternative medicine to treat various diseases. From a biological perspective, puerarin can be described as a white needle crystal with the chemical name of 7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one-8-D-glucopyranoside. Besides, puerarin is sparingly soluble in water and produces no color or light yellow solution. Multiple experimental and clinical studies have confirmed the significant therapeutic effects of puerarin. These effects span a wide range of pharmacological effects, including neuroprotection, hepatoprotection, cardioprotection, immunomodulation, anticancer properties, anti-diabetic properties, anti-osteoporosis properties, and more. Puerarin achieves these effects by interacting with various cellular and molecular pathways, such as MAPK, AMPK, NF-κB, mTOR, ß-catenin, and PKB/Akt, as well as different receptors, enzymes, and growth factors. The current review highlights the molecular mechanism of puerarin as a neuroprotective agent in the treatment of various neurodegenerative and neurological diseases. Extensive cellular, animal, and clinical research has provided valuable insights into its effectiveness in conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, cerebral stroke, depression, and more.

2-Bromo-3-hy-droxy-6-methyl-pyridine.

In the title compound, C6H6BrNO, the Br atom is displaced from the pyridine ring mean plane by 0.0948 (3) Å, while the hydroxyl O atom and the methyl C atom are displaced by 0.0173 (19) and 0.015 (3) Å, respectively. In the crystal, mol-ecules are linked via O-H⋯N hydrogen bonds, forming chains propagating along the a-axis direction. These chains are linked by C-H⋯Br hydrogen bonds, forming corrugated two-dimensional networks lying parallel to the ac plane.

Micropropagation of seedless lemon (Citrus limon L. cv. Kaghzi Kalan) and assessment of genetic fidelity of micropropagated plants using RAPD markers.

A micropropagation protocol was developed for multiplication of seedless lemon (Citrus limon L. cv. Kaghzi Kalan) using nodal explants. The maximum shoot regeneration was observed on low level of BAP (0.1 mg l(-1)) or kinetin (0.5 mg l(-1)). BA was recorded to be better than kinetin in terms of number of days taken to bud break. The maximum number of shoots per explant was observed on 0.1 mg l(-1) BA and 0.5 mg l(-1) kinetin. Shoot proliferation decreased with increasing concentration of BA alone, but in case of a combination of BA and NAA (0.1 mg l(-1) each), it increased with increasing concentration of BA up to 10.0 mg l(-1). None of the treatments including BA or kinetin alone or BA in combination with NAA produced significantly more shoots for commercial exploitation. In the case of a combination of BA + kinetin + IBA, the maximum (5.5 shoots per explants) proliferation was observed on MS medium containing 1.0 mg l(-1) BA + 0.5 mg l(-1) kinetin + 0.5 mg l(-1) IBA or 0.25 mg l(-1) BA + 1.0 mg l(-1) kinetin + 1.0 mg l(-1) IBA. Regenerated shoots showed root induction on MS basal medium or on MS medium containing 1.0 mg l(-1) IBA. It is concluded that a five-fold increase (1.0 mg l(-1) BA + 0.5 mg l(-1) kinetin + 0.5 mg l(-1) IBA) in axillary shoot proliferation, while seven-fold increase (0.25 mg/l mg l(-1) BA + 1.0 mg l(-1) kinetin + 1.0 mg l(-1) IBA) during the second cycle of multiplication could be obtained using the two plant growth regulator combinations. PCR amplification with 14 different random primers confirmed no somaclonal variant up to two cycles of shoot multiplication.

Effect of gamma radiation on microbial safety and nutritional quality of kachri (Cucumis callosus).

Fresh dried and old (6-12 months) dried kachri (Cucumis callosus) were treated with 0, 2.5, 5 and 7 kGy of gamma radiation in a cobalt 60 gamma cell (GC-1200). The irradiated samples of kachri were stored at room temperature (28 ± 2 °C). Total bacterial count and nutrient composition were evaluated immediately after irradiation and at regular intervals of 1 month during 3 months of storage. Results indicated that gamma radiation reduced the total bacterial counts of dried samples of both fresh and old dried kachri. Dose of 5.0 kGy was sufficient to eliminate total bacterial count and there was no microbial growth in 5.0 kGy irradiated samples during the storage period. No significant differences were observed in the proximate composition of both types of kachri at all irradiation doses. It was concluded that irradiation treatments of kachri improves keeping quality of both freshly dried and old dried Kachri.

Pharmacological potential of zonisamide and Nigella sativa per se and combination in high-impact trauma device-induced traumatic brain injury in Drosophila melanogaster.

Traumatic brain injury (TBI) is a public health menace responsible for millions of fatalities and disabilities. Numerous drugs available provide symptomatic relief but cannot stop the progress of secondary injury; thus, it is required to discover newer therapeutic agents that protect neuronal damage after trauma, predominantly in secondary injury. Thus the present study was designed to study the pharmacological potential of zonisamide and Nigella sativa (NS) per se and in combination, using high-impact trauma device (HIT)-induced TBI model in Drosophila melanogaster (fruit flies). Oregon R+ strains of fruit flies were pre-treated, 24 h before TBI, with different concentrations of zonisamide, NS, and their combination. The mortality rate was observed at 0 h, 6 h, and 24 h, followed by measurement of locomotor activity using climbing assay after 6 h and 24 h of TBI. Furthermore, the level of AChE and various neurotransmitters were measured along with different oxidative stress parameters at 24 h after the injury. Administration of zonisamide and NS significantly reduced mortality rate and improved locomotor activity. Both zonisamide and NS elevate levels of AChE, GABA, serotonin, and dopamine level in fruit flies, along with a significant reduction in glutamate levels. Moreover, a concentration-dependent elevation in SOD, GSH, and catalase level and a decrease in MDA and nitrite levels were observed. Co-administration of zonisamide and NS showed tremendous neuroprotective potential by lowering behavior impairments, oxidative damages, and restoring altered neurotransmitter levels in fruit flies compared with individual administration and thus can employ as a better therapeutic medicine for the treatment of TBI.

Hydropower: A low-hanging sour-sweet energy option for India.

India is the world's second largest populous nation, fifth largest economy with seventh largest geographical area but experiences high energy poverty. With the lowest per capita energy consumption among world's top ten economies, India ranks at 137 out of 218 nations. Hydropower has the potential to alleviate India's energy asymmetry as well as realize its sustainable growth aspiration of a low-carbon regime. However, hydropower in India has been plagued by debates on human displacement, loss of biodiversity, increased risk of natural disasters, and socio-economic conflicts making it an unpopular energy alternative. Here, we review and address various concerns related to India's hydropower sector, examine scientific evidence, analyze energy policy imperatives, geopolitical considerations, and future directions for a sustainable hydropower policy in India in the context of ongoing climate change. Evidence indicates that besides electricity generation, hydropower infrastructure helps: (i) avert floods, (ii) mitigate the impacts of global warming, and (iii) ensure redistribution of water to arid regions and improve water security. As a part of sustainable hydropower policy, we propose that most of the ecological and social problems associated with hydropower development can be avoided to a great extent through careful planning, proper project design, responsible ownership, and public participation. As short-term measures, we propose: (i) entrepreneurs and planners follow credible and transparent pre-project investigations, (ii) mandatory implementation of environmental management plans, and (iii) better accountability and transparency of statutory bodies as well as hydropower developers. For long-term measures, we suggest: (i) create a 'National Institute of Energy & Environmental Sustainability' to oversee post-project hydropower developmental activities, (ii) streamline various bureaucratic and institutional procedures, and (ii) establish a trans-boundary water management system for seamless and coordinated implementation of hydropower development programs across upstream-downstream nations.