Nitin Kumar

Hypericum perforatum L. is a well-documented medicinal plant traditionally used for neurological and inflammatory disorders. However, comprehensive quality standardization and mechanistic validation of its root extracts is prohibited. The present study aimed to establish pharmacognostical and phytochemical standardization for Hypericum perforatum roots and to elucidate their potential antiepileptic properties using an integrated analytical and bioinformatic approach. Pharmacognostical evaluation included physicochemical parameters, such as ash values and extractive values, supported by qualitative phytochemical screening. Regarding densitometric profiling and quantitative quercetin quantification, high-performance thin-layer chromatography was employed, ensuring batch-to-batch consistency and confirmation of marker compounds. Comprehensive characterization of metabolites proved possible by liquid chromatography–mass spectrometry analysis, which validated the physical presence of important biologically active compounds, such as rutin, quercetin, kaempferol, gallic acid, and ferulic acid. To explore the molecular basis of antiepileptic activity, identified phytochemicals were subjected to network pharmacology investigation. In network pharmacology, protein–protein interaction and enhancement investigation revealed the key targets, such as prostaglandin-endoperoxide synthase 2 (PTGS2), AKT1, epidermal growth factor receptor (EGFR), ESR1, BCL2, and SRC, which were involved in neuronal excitability, oxidative stress, inflammation, and apoptotic regulation. Integrated Kyoto Encyclopedia of Genes and Genomes and gene ontology analysis highlighted estrogen signaling, EGFR-related pathways, oxidative stress response, and kinase-mediated signaling as major mechanisms relevant to epilepsy.

Background: Treatment for hepatic complications still remains a challenging issue for healthcare professionals due to lack of multitargeted and biomolecular-based therapeutic approaches. Moreover, contemporary therapeutic approaches often fail to achieve widespread and sustained utilization due to limitations related to affordability, accessibility and availability. Terminalia arjuna (Roxb. ex DC.) Wight & Arn., a well-known Indian medicinal plant, is recognized for its antioxidant, anti-inflammatory, and cardioprotective properties. Objectives: This study aims to explore the metabolomic profiling (HPTLC and LC-MS) and network pharmacology–based biomolecular targets of T. arjuna in the treatment of hepatic disease. Methodology: Pharmacopoeial assessment was conducted to establish quality standards, and DPPH antioxidant activity was analyzed to evaluate free radical scavenging. Phytochemical insights and biomolecular approaches were revealed through HPTLC and LC-MS technique and network pharmacology analysis. Network pharmacology and gene ontology analyses further examined the plant’s multitargeted effects on hepatic disorders. Results: The results confirmed that T. arjuna meets pharmacopoeial quality standards, with notable DPPH radical scavenging activity (IC50 = 182.2 ± 1.846 μg/mL). Metabolomic analysis revealed significant marker compounds, while network pharmacology identified TP53, IL6, and HFE as primary targets interacting with gallic acid, ellagic acid, arjunolic acid, procyanidin, and catechin. These interactions regulate liver carcinoma, hepatocellular carcinoma risk, hypogammaglobulinemia, and liver cirrhosis. Conclusion: The study concludes that T. arjuna effectively modulates TP53, IL6, and HFE expression, providing a promising natural approach for liver disorders. However, further preclinical and clinical studies are needed to bridge existing scientific gaps and validate its therapeutic efficacy.

Thioacetamide (TAA), an established liver toxic chemical, is used to develop experimental models of liver injury by inducing inflammation, oxidative stress, and apoptosis. The current study investigates the hepatoprotective effect of diosmetin (DSM), a bioflavonoid molecule, with mechanistic investigations using an in vivo TAA-induced liver injury model because there is no precedence. In the current investigation, 30 Wistar rats were randomly assigned to five groups. The rats were given TAA (200 mg/kg) and DSM (50 and 100 mg/kg body weight) for 8 weeks. Liver function biomarkers (ALT, ASP, AST, bilirubin, GGT, CRP, albumin, globulin, and total protein) and inflammatory markers were analyzed on serum, whereas antioxidant levels, histological evaluation, and apoptotic markers were evaluated on liver tissue. The finding of this study indicated that DSM ameliorates TAA-induced increases in ALT, ASP, AST, bilirubin, GGT, CRP, MDA, albumin, globulin, total protein, and antioxidant enzyme activity such as SOD, CAT, and GSH levels. DSM reduced alterations in inflammatory biomarkers (IL-6, IL-1β, TNF-α) and apoptotic markers (Bax, NF-κB, caspase-3, Nrf-2, PPAR_ϒ) in liver tissues. Furthermore, DSM therapy resulted in significant major changes in liver histology, fibrosis, and cell death. The current study’s findings demonstrated that DSM significantly decreases hepatotoxicity by enhancing liver structure and function while suppressing oxidative stress, inflammation, and apoptosis.

This study aimed to develop a delivery system for the dried aqueous extract of Rubia cordifolia leaves (RCE) that could improve the neuroprotective potential of RCE by improving the bioavailability of the chief chemical constituent rubiadin. Rubiadin, an anthraquinone chemically, is a biomarker phytoconstituent of RCE. Rubiadin is reported to have strong antioxidant and neuroprotective activity but demonstrates poor bioavailability. In order to resolve the problem related to bioavailability, RCE and phospholipids were reacted in disparate ratios of 1:1, 1:2, and 1:3 to prepare phytosome formulations PC1, PC2, and PC3, respectively. The formulation PC2 showed particle size of 289.1 ± 0.21 nm, ζ potential of -6.92 ± 0.10 mV, entrapment efficiency of 72.12%, and in vitro release of rubiadin of 89.42% at pH 7.4 for a period up to 48 h. The oral bioavailability and neuroprotective potential of PC2 and RCE were assessed to evaluate the benefit of PC2 formulation over the crude extract RCE. Formulation PC2 showed a relative bioavailability of 134.14% with a higher neuroprotective potential and significantly (p < 0.05) augmented the nociceptive threshold against neuropathic pain induced by partial sciatic nerve ligation method. Antioxidant enzyme levels and histopathological studies of the sciatic nerves in various treatment groups significantly divulged that PC2 has enough potential to reverse the damaged nerves into a normal state. Finally, it was concluded that encapsulated RCE as a phytosome is a potential carrier system for enhancing the delivery of RCE for the efficient treatment of neuropathic pain.

Background: Diabetic neuropathy is a debilitating manifestation of long-term diabetes mellitus. The present study explored the effects of the roots of Rubia cordifolia L. (R. cordifolia L.) in the Wistar rat model for diabetic neuropathy and possible neuroprotective, antidiabetic, and analgesic mechanisms underlying this effect. Materials and Methods: Rats were divided into five experimental groups. An amount of 0.25% carboxy methyl cellulose (CMC) in saline and streptozotocin (STZ) (60 mg/kg) was given to group 1 and group 2, respectively. Group 3 was treated with STZ and glibenclamide simultaneously while groups 4 and 5 were simultaneously treated with STZ and hydroalcoholic extract of the root of R. cordifolia, respectively. Hot plate and cold allodynias were used to evaluate the pain threshold. The antioxidant effects of R. cordifolia were assessed by measuring Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). At the end of the study, sciatic nerve and brain tissues were collected for histopathological study. Bcl-2 proteins, cleaved caspase-3, and Bax were assessed through the Western blot method. Results: R. cordifolia significantly attenuated paw withdrawal and tail flick latency in diabetic neuropathic rats. R. cordifolia significantly (p < 0.01) improved the levels of oxidative stress. It was found to decrease blood glucose levels and to increase animal weight in R. cordifolia-treated groups. Treatment with R. cordifolia suppressed the cleaved caspase-3 and reduced the Bax:Bcl2 ratio in sciatic nerve and brain tissue compared to the diabetic group. Histopathological analysis also revealed a marked improvement in architecture and loss of axons in brain and sciatic nerve tissues at a higher dose of R. cordifolia (400 mg/kg). Conclusion: R. cordifolia attenuated diabetic neuropathy through its antidiabetic and analgesic properties by ameliorating apoptosis and oxidative stress.

This work aimed to encapsulate Hypericum perforatum extract (HPE) into nanophytosomes (NPs) and assess the therapeutic efficacy of this nanocarrier in neuropathic pain induced by partial sciatic nerve ligation (PSNL). Hydroalcoholic extract of Hypericum perforatum was prepared and encapsulated into NPs by thin layer hydration method. Particle size, zeta potential, TEM, differential scanning calorimetry (DSC), entrapment efficiency (%EE), and loading capacity (LC) of NPs were reported. The biochemical and histopathological examinations were measured in the sciatic nerve. Particle size, zeta potential, %EE, and LC were 104.7 ± 1.529 nm, -8.93 ± 1.71 mV, 87.23 ± 1.3%, and 53.12 ± 1.7%, respectively. TEM revealed well-formed and distinct vesicles. NPHPE (NPs of HPE) was significantly more effective than HPE in reducing PSNL-inducing pain. Antioxidant levels and sciatic nerve histology were reversed to normal with NPHPE. This study demonstrates that encapsulating HPE with phytosomes is an effective therapeutic approach for neuropathic pain.

Objectives: Pitavastatin is a competitive HMG-CoA reductase inhibitor for lowering of cholesterol level and low density lipoprotein cholesterol. This study was designed to evaluate the effect of pitavastatin in neuropathic pain induced by partial sciatic nerve ligation along with neuronal changes in Wister rats. Methods: Pitavastatin was started three days prior to the surgery and continued for 14 days The pain was determined by thermal hyperalgesia and cold allodynia. The biochemical changes were estimated at the end of the study. The levels of cytokines were measured using an ELISA test. Western blot analysis was used to detect levels of expression of JNK, p-JNK, ERK, p-ERK, p38MAPK, p-p38MAPK. The sciatic nerve was investigated histopathologically. Key findings: Pitavastatin significantly ameliorated nerve pain induced by PSNL and also attenuated the biochemical changes in a dose-dependent manner. The levels of inflammatory mediators were inhibited by pitavastatin. There was significant improvement in sciatic nerve fibres histology. The levels of p-38, p-ERK, and p-JNK and their associated phosphorylated proteins were reduced after treatment with pitavastatin. Conclusion: The present study indicates that treatment with pitavastatin reversed the PSNL-induced neuropathy in Wister rats and may be an additional therapeutic strategy in the management of neuropathic pain.

Trichosanthes , a genus of family Cucurbitaceae, is an annual or perennial herb distributed in tropical Asia and Australia. Pointed gourd (Trichosanthes dioica Roxb.) is known by a common name of parwal and is cultivated mainly as a vegetable. Juice of leaves of T. dioica is used as tonic, febrifuge, in edema, alopecia, and in subacute cases of enlargement of liver. In Charaka Samhita, leaves and fruits find mention for treating alcoholism and jaundice. A lot of pharmacological work has been scientifically carried out on various parts of T. dioica, but some other traditionally important therapeutical uses are also remaining to proof till now scientifically. According to Ayurveda, leaves of the plant are used as antipyretic, diuretic, cardiotonic, laxative, antiulcer, etc. The various chemical constituents present in T. dioica are vitamin A, vitamin C, tannins, saponins, alkaloids, mixture of noval peptides, proteins tetra and pentacyclic triterpenes, etc.