Syringin from Tinospora crispa downregulates pro-inflammatory mediator production through MyD88-dependent pathways in lipopolysaccharide (LPS)-induced U937 macrophages.

BACKGROUND: Syringin, a phenylpropanoid glycoside, has exhibited numerous biological properties including inhibitory activities against various immune and inflammatory disorders. In this study, syringin isolated from Tinospora crispa was evaluated for its ability to down-regulate activated nuclear factor-kappa B (NF-κB), phosphoinositide-3-kinase-Akt (PI3K-Akt) and mitogen-activated protein kinases (MAPKs) signal transducing networks in U937 macrophages activated by lipopolysaccharide. METHODS: The attenuating effects of syringin on the productions of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α), and the expressions of signaling molecules of the signaling pathways were investigated by using ELISA, Western blot, and qRT-PCR. RESULTS: Syringin downregulated the NF-κB, MAPKs, and PI3K-Akt signal networks by significantly reducing PGE2 production in the macrophages via suppression of COX-2 gene and protein expression levels. It also reduced TNF-α and IL-1ß secretion and their mRNA expression, suppressed phosphorylation of NF-κB (p65), IKKα/ß, and IκBα, and restored ability of IκBα to degrade. Syringin dose-dependently attenuated Akt, p38 MAPKs, JNK, and ERK phosphorylation. Also, the expression of corresponding upstream signaling molecules toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) were down-regulated in response to syringin treatment. CONCLUSION: The suppressive effect of syringin on the inflammatory signaling molecules in MyD88-dependent pathways suggested it's potential as a drug candidate for development into an agent for treatment of various immune-mediated inflammatory disorders.

Structural Revision of Tinotufolins from Tinospora crispa Leaves Guided by Empirical Rules and DFT Calculations.

Clerodane diterpenes are a class of secondary metabolites that can be classified into four types according to the configuration of the H3-19/H-10-H3-17/H3-20 fragment, i.e., trans-cis (TC), trans-trans (TT), cis-cis (CC), and cis-trans (CT). Tinotufolins A-C and E (1a-3a and 5a), isolated from the leaves of Tinospora crispa, were previously elucidated as CT-type clerodanes; however, our established 13C NMR-based empirical rules and density functional theory calculations suggested that these clerodanes belong to the CC type. Therefore, tinotufolins A-F (1-6) were reisolated from the leaves of T. crispa, along with an undescribed compound 7 and known compounds 8-11, and their structures were established by extensive spectroscopic analyses. The structures of tinotufolins A-C and E were revised to CC-type 1-3 and 5, and undescribed compound 7 was established as a CC-type clerodane. The present study demonstrates that empirical rules and calculations can efficiently identify and revise erroneous structures in clerodane diterpenes.

Determination of genoprotection against cyclophosphamide induced toxicity in bone marrow of Swiss albino mice by Moringa oleifera leaves and Tinospora cordifolia stem.

The present study aimed to determine the genoprotective activity and safety of Moringa oleifera leave and Tinospora cordifolia stem extracts against cyclophosphamide (CP)-induced genotoxicity utilizing Swiss albino mice. Animals were divided into 14 groups for subacute treatment with either M. oleifera or T. cordifolia extracts daily for 28 days. The extract doses selected were 100, 200 or 400 mg/kg b.w administered orally alone or combined with CP (50 mg/kg b.w. intraperitoneally daily for 5 days). Analyses performed included the comet assay, micronucleus test (MN) in bone marrow cells and sperm head abnormality assay (SHA). M. oleifera and T. cordifolia extracts induced no significant genotoxic effects on somatic and germ cells. In contrast, for all cells examined M. oleifera and T. cordifolia extracts inhibited DNA damage initiated by CP. Taken together data demonstrated that both plant extracts did not exhibit marked genotoxic effects but displayed potential chemoprotective properties against CP-induced genotoxicity in Swiss mice.

Three neo-Clerodane Diterpenoids from Tinospora cordifolia Stems and Their Arginase Inhibitory Activities.

Three neo-clerodane diterpenoids, including two new tinocordifoliols A (1) and B (2) and one known tinopanoid R (3), were isolated from the ethyl acetate-soluble fraction of the 70% ethanol extract of Tinospora cordifolia stems. The structures were elucidated by various spectroscopic methods, including one dimensional (1D) and 2D-NMR, high resolution-electrospray ionization (HR-ESI)-MS, and electronic circular dichroism (ECD) data. The T. cordifolia extract and all isolated compounds 1-3 possessed arginase I inhibitory activities. Among them, 3 exhibited moderate competitive inhibition of human arginase I (IC50 = 61.9 µM). Furthermore, docking studies revealed that the presence of a ß-substituted furan in 3 may play a key role in the arginase I inhibitory activities.

A Review on Traditional Uses, Phytochemistry, Pharmacology and Clinical Application of Tinospora sinensis (Lour.) Merr.

Tinospora sinensis (T. sinensis), whose Tibetan name is "Lezhe", as a traditional medicine, is widely distributed in China, India and Sri Lanka. It is used for the treatment of rheumatic arthralgia, sciatica, lumbar muscle strain and bruises. Research over the previous decades indicated that T. sinensis mainly contains terpenes, lignans, alkaloids, phenol glycosides and other chemical components. A wide range of pharmacologic activities such as anti-inflammatory, analgesic, immunosuppressive, anti-aging, anti-radiation, anti-leishmania and liver protection have been reported. However, the scholar's research on the pharmacodynamic material basis of T. sinensis is relatively weak. Data regarding many aspects such as links between the traditional uses and bioactivities, pharmacokinetics, and quality control standard of active compositions is still limited and need more attention. This review reports a total of 241 compounds, the ethnopharmacology and clinical application of T. sinensis, covering the literature which were searched by multiple databases including Web of Science, PubMed, Google Scholar, Science Direct, CNKI and other literature sources from 1996 to date, with a view to provide a systematic and insightful reference and lays a foundation and inspiration for the application and further in-depth research of T. sinensis resources.

Biosynthesis and biological activities of magnesium hydroxide nanoparticles using Tinospora cordifolia leaf extract.

The synthesis of magnesium hydroxide nanoparticles (Mg(OH)2 NPs) using plant extracts are known to be a practical, economical, and an environmentally friendly approach. In this work, Mg(OH)2 NPs were synthesized using aqueous leaf extract of Tinospora cordifolia, a medicinal plant commonly found in India. The synthesized Mg(OH)2 NPs were characterized using various spectroscopic techniques. The ultraviolet-visible (UV-Vis) absorption peak of the Mg(OH)2 NPs was detected at 289 nm, Fourier transform infrared (FTIR) analysis confirmed the presence of various functional groups, and X-ray diffraction (XRD) patterns revealed the well-crystallized structure of the Mg(OH)2 NPs. High-resolution transmission electron microscopy (HR-TEM) and scanning electron microscopy (SEM) analyses depicted spherical morphology and an average particle size (PS) of 27.71 nm. The energy-dispersive X-ray (EDX) analysis confirmed the presence of C, O, and Mg elements, and the X-ray photoelectron spectroscopy (XPS) survey spectrum confirmed the elements for the Su 1 s peak at 280.2 eV. The dynamic light scattering (DLS) analysis displayed an average PS of 54.3 nm, and the Zeta potential (ZP) was of 9.89 mV. The fabricated Mg(OH)2 NPs displayed notable antibacterial activity against S. epidermidis, E. coli, and S. aureus. In addition, these NPs exhibited strong antioxidant properties (> 75%) based on DPPH, ABTS, and hydrogen peroxide (H2O2) assays. Further, the same NPs exerted a potent anti-inflammatory activity (> 65%) based on COX-1 and COX-2 evaluations. The anti-Alzheimer' disease (AD) potential of Mg(OH)2 NPs was assessed through effective inhibition (> 70%) of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities. Molecular docking (MD) studies confirmed that caryophyllene has higher binding affinity with AChE (-5.3 kcal/mol) and BuChE (-6.4 kcal/mol) enzymes. This study emphasizes the green synthesis of Mg(OH)2 NPs using T. cordifolia as a plant source and highlights their potential for biomedical applications.

Process Optimization of Tinospora cordifolia Extract-Loaded Water in Oil Nanoemulsion Developed by Ultrasound-Assisted Homogenization.

Nanoemulsions are gaining interest in a variety of products as a means of integrating easily degradable bioactive compounds, preserving them from oxidation, and increasing their bioavailability. However, preparing stable emulsion compositions with the desired characteristics is a difficult task. The aim of this study was to encapsulate the Tinospora cordifolia aqueous extract (TCAE) into a water in oil (W/O) nanoemulsion and identify its critical process and formulation variables, like oil (27-29.4 mL), the surfactant concentration (0.6-3 mL), and sonication amplitude (40% to 100%), using response surface methodology (RSM). The responses of this formulation were studied with an analysis of the particle size (PS), free fatty acids (FFAs), and encapsulation efficiency (EE). In between, we have studied a fishbone diagram that was used to measure risk and preliminary research. The optimized condition for the formation of a stable nanoemulsion using quality by design was surfactant (2.43 mL), oil concentration (27.61 mL), and sonication amplitude (88.6%), providing a PS of 171.62 nm, FFA content of 0.86 meq/kg oil and viscosity of 0.597 Pa.s for the blank sample compared to the enriched TCAE nanoemulsion with a PS of 243.60 nm, FFA content of 0.27 meq/kg oil and viscosity of 0.22 Pa.s. The EE increases with increasing concentrations of TCAE, from 56.88% to 85.45%. The RSM response demonstrated that both composition variables had a considerable impact on the properties of the W/O nanoemulsion. Furthermore, after the storage time, the enriched TCAE nanoemulsion showed better stability over the blank nanoemulsion, specially the FFAs, and the blank increased from 0.142 to 1.22 meq/kg oil, while TCAE showed 0.266 to 0.82 meq/kg.

De novo genome assembly and annotation of the medicinal plant Tinospora cordifolia (Willd.) Miers ex Hook. f. & Thom's.

Indian natural climbing shrub Tinospora cordifolia, often known as "Guduchi" and "Amrita," is a highly esteemed medicinal plant in the Indian system of medicine (ISM). It is a member of the Menispermaceae family which consists of a rich source of protein, micronutrients, and rich source of bioactive components which are used in treating various systemic diseases. The current study was designed to know the biological characterization of the plant genome and biosynthesis of plant metabolites essential for its medicinal applications. Tinospora cordifolia's complete genome was sequenced using Illumina HiSeq2500 sequencing technology. The draft genome was assembled through a de novo method. An integrative genome annotation approach was used to perform functional gene prediction. The pathway analysis was carried out using the KEGG database. The total genome size obtained after genome assembly was 894 Mb with an N50 of 9148 bp. The integrative annotation approach resulted in 35,111 protein-coding genes. In addition, genes responsible for the synthesis of syringin, a secondary metabolite found in plants, were identified. In comparison to the standard drug (dopamine, rasagiline, and selegiline), syringin's molecular docking exhibited a greater binding affinity from the range of - 4.3 to - 6.6 kcal/mol for all the targets of Parkinson's disease and for Alzheimer's targets; it has shown the maximum potency from the range of - 6.5 to - 7.4 kcal/mol with respect to the standard drug (donepezil, galantamine, and rivastigmine). This study provides the genomic information of Tinospora cordifolia which is helpful in understanding genomic insights and metabolic pathways connected to the corresponding plant genome and predicts the possible useful effect for the molecular characterization of therapeutic drugs.

Diterpenoids and Their Glycosides from the Stems of Tinospora crispa with Beta-Cell Protective Activity.

Seven previously undescribed diterpenoids, tinocrisposides A-D (1-4) and borapetic acids A (5), B (6), and C (7), together with 16 known compounds, were isolated from the stem of Tinospora crispa (Menispermaceae). The structures of the new isolates were elucidated by spectroscopic and chemical methods. The ß-cell protective effect of the tested compounds was examined on insulin-secreting BRIN-BD11 cells under dexamethasone treatment. Diterpene glycosides 12, 14-16, and 18 presented a substantial protective effect on BRIN-BD11 cells treated with dexamethasone in a dose-dependent manner. Compounds 4 and 17 with two sugar moieties exhibited clear protective effects on ß-cells.

Tinopanoids K-T, clerodane diterpenoids with anti-inflammatory activity from Tinospora crispa.

A total of 17 structurally diverse clerodane diterpenoids, including ten undescribed clerodane diterpenoids (tinopanoids K-T, 1-10) and seven known compounds (11-17), were isolated from the vines and leaves of Tinospora crispa. Compound 3 has not only bear the dominant substituents of γ-hydroxy-α, ß-unsaturated-γ-lactone with anti-inflammatory activity, but also a ternary epoxy structure at C-3/C-4. The planar structures and relative configurations of the clerodane diterpenoids were elucidated by spectroscopic data interpretation. The absolute configurations of compounds 1, 4, 8 and 13 were determined by single-crystal X-ray crystallographic, while that of compound 3 was determined using computed ECD data and single crystal X-ray diffraction of related p-bromobenzoate ester (3a). Subsequently, all compounds were evaluated for their inhibitory effect on nitric oxide (NO) production of LPS-activated BV-2 cells, and compounds 3 and 8 exhibited better NO inhibitory potency, with IC50 values of 5.6 and 13.8 µM than the positive control minocycline (Mino, IC50 = 22.9 µM). The corresponding results of western blot analysis and qRT-PCR revealed that compound 3 can significantly inhibit the inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expressions, mRNA levels of pro-inflammatory cytokins of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and interleukin 1ß (IL-1ß). The underlying mechanism by which compound 3 exerted anti-neuroinflammatory effects was investigated by western blot and immunofluorescence assay, which suggested compound 3 inhibited LPS induced neuroinflammation via the suppression of toll-like receptor 4 (TLR4) dependent Signal Transducer and Activator of Transcription 3 (Stat3) and mitogen-activated protein kinase (MAPK) signaling pathways, and the activation of Heme Oxygenase-1 (HO-1) mediated signals.

Tinospora cordifolia modulates the seminal parameters, leakage of intracellular enzymes and seminal antioxidants in equilibrated and cryopreserved semen of Sahiwal bulls.

The present study was undertaken to assess the effects of stem extract of Tinospora cordifolia (Giloy or Guduchi) in the semen extender on seminal parameters, leakage of intracellular enzymes and antioxidants in semen of Sahiwal bull. A total of 48 ejaculates from four bulls were selected for the study. Spermatozoa of 25 × 106 were incubated in 100, 300 and 500 µg of stem extract of Guduchi as Gr II, III and IV, respectively, and pre-freeze and post-thaw semen samples were analysed for seminal parameters [motility, viability, total sperm abnormality (TSA), plasma membrane integrity (PMI) and acrosomal integrity (AcI)], intracellular enzymes [aspartate aminotransferase (AST) and lactate dehydrogenase (LDH)] and seminal antioxidants [superoxide dismutase (SOD) and catalase] in comparison with an untreated control group (Gr I). The results revealed that stem extract-treated semen had significantly (p < .05) higher motility, viability, PMI, AcI, SOD and catalase and had significantly (p < .05) lower TSA, AST and LDH compared to those in untreated control group at pre-freeze and post-thaw stages. Semen treated with 100 µg stem extract/25 × 106 spermatozoa had significantly (p < .05) higher motility, viability, PMI, AcI, SOD and catalase and had significantly (p < .05) lower TSA, AST and LDH compared to those in control, 300- and 500-µg-treated groups at pre-freeze and post-thaw stages. Further, these seminal parameters and antioxidants were showing decreasing trend and TSA and leakage of intracellular enzymes were showing increasing trend from Gr II to Gr IV at pre-freeze and post-thaw stages. Thus, 100 µg/25 × 106 spermatozoa were optimum or suitable dose for cryopreservation of Sahiwal bull semen. The study concluded that T. cordifolia stem extract 100 µg/25 × 106 spermatozoa in the semen extender can be effectively utilized to reduce the oxidative stress and improve the pre-freeze and post-thaw seminal parameters in Sahiwal bull. However, further studies on effects of different concentrations of stem extract on in vitro or in vivo fertility trials are to be conducted to assess the impact of the stem extract supplementation in the semen extender on field pregnancy outcomes in bovine species.

Constituents of Tinospora sinensis and their nitric oxide inhibitory activities.

One new phenylpropanoid glycoside, tinosinen A (1) and 13 known compounds, tinosinen (2), citrusin B (3), picraquassioside C (4), erythro-guaiacylglycerol-ß-O-4'-coniferyl alcohol (5), erythro-guaiacylglycerol-8-O-4'-(sinapyl alcohol) ether (6), erythro-syringylglycerol-8-O-4'-(sinapyl alcohol) ether (7), seco-isolariciresinol 9-O-D-ß-glucopyranoside (8), tinosposide A (9), pinoresinol-4'-O-ß-D-glucopyranoside (10), syringaresinol-4'-O-ß-D-glucopyranoside (11), pinoresinol (12), syringaresinol (13), and lirioresino-ß-dimethyl ether (14) were isolated from the stems of Tinospora sinensis (Lour.) Merr. Their structures were established by detailed spectroscopic studies and comparisons with those reported in the literature. Compound 13 showed significant inhibitory NO production (IC50 value of 38.53 ± 1.90 µM) in RAW264.7 macrophages, LPS-stimulated. Compounds 3-7, 11, 12, and 14 inhibited NO production with IC50 values ranging from 38.53 to 99.07 µM.

Effect of Tinospora cordifolia on gestational diabetes mellitus and its complications.

Ayurvedic system of medicine uses giloy or guduchi, also known as Tinospora cordifolia (TC), to treat diabetes and related diseases like hyperglycemia and hyperlipididemia. However, its usage in gestational diabetes mellitus (GDM) is not well studied. The primary objective of the study was to examine the effects of water extract of TC called satva, essential oil, and hydroalcoholic (HA) extract on GDM and its complications and to explore their mechanism of action using mice model. We used streptozotocin-induced diabetes in pregnant mice as murine model and tested TC preparations for anti-GDM activities. Blood glucose, insulin, litter size, and placental weight were assessed. ELISA method was used to measure plasma insulin level to compute homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and homeostatic model assessment for assessing beta cell function (HOMA-Beta) levels to estimate insulin resistance, insulin sensitivity, and beta cell function respectively. TC-treated groups had significantly higher serum insulin levels, QUICKI, average litter size, and lower placental weight (p < .001). TC oil and HA extract increased pancreatic beta cell activity according to the level of HOMA-Beta. TC lowered placenta weight and increased litter size significantly compared to control group. Our findings suggest that TC preparations preserve pancreatic beta cells, increase insulin production, decrease insulin resistance, and improve beta cell function, hence preventing GDM. TC preparations also reduced placental weight and increased litter size in mice. Based on these results, we recommend the clinical trial and testing of TC preparations for management of GDM and associated complications. Refer graphical abstract (Figure S1).

Unveiling Various Facades of Tinospora cordifolia Stem in Food: Medicinal and Nutraceutical Aspects.

Natural products with curative properties are gaining immense popularity in scientific and food research, possessing no side effects in contrast to other drugs. Guduchi, or Tinospora cordifolia, belongs to the menispermaceae family of universal drugs used to treat various diseases in traditional Indian literature. It has received attention in recent decades because of its utilization in folklore medicine for treating several disorders. Lately, the findings of active phytoconstituents present in herbal plants and their pharmacological function in disease treatment and control have stimulated interest in plants around the world. Guduchi is ethnobotanically used for jaundice, diabetes, urinary problems, stomachaches, prolonged diarrhea, skin ailments, and dysentery. The treatment with Guduchi extracts was accredited to phytochemical constituents, which include glycosides, alkaloids, steroids, and diterpenoid lactones. This review places emphasis on providing in-depth information on the budding applications of herbal medicine in the advancement of functional foods and nutraceuticals to natural product researchers.

Clerodane Furanoditerpenoids from Tinospora bakis (A.Rich.) Miers (Menispermaceae).

Tinospora bakis (A.Rich.) Miers (Menispermaceae) has traditionally been used to alleviate headaches, rheumatism, mycetoma, and diabetes, among others. Despite its extensive use, the active components of the plant have never been investigated. In this work, a series of furanoditerpenoids (1-18) and five compounds from other classes (19-23) were isolated from T. bakis. Notably, two new compounds were discovered and named: tinobakisin (1) and tinobakiside (10). Their molecular structures were elucidated with NMR, MS, UV, IR, and ECD spectra. Additionally, known compounds (2-9 and 11-23) were corroboratively identified through spectral comparisons with previously reported data, while highlighting and addressing some inaccuracies in the prior literature. Remarkably, compounds 6, 7, 13, and 17 exhibited a superior anti-glycation effect, outperforming established agents like rutin and quercetin in a lab model of protein glycation with glucose. The overall findings suggest that furanoditerpenoids play a crucial role in the antidiabetic properties of T. bakis. This research marks the first comprehensive phytochemical investigation of T. bakis, opening the door for further investigation into furanoditerpenoids and their biological mechanisms.

Tinosporaside from Tinospora cordifolia Encourages Skeletal Muscle Glucose Transport through Both PI-3-Kinase- and AMPK-Dependent Mechanisms.

The stem of Tinospora cordifolia has been traditionally used in traditional Indian systems of medicine for blood sugar control, without the knowledge of the underlying mechanism and chemical constitution responsible for the observed anti-diabetic effect. In the present study, Tinosporaside, a diterpenoid isolated from the stem of T. cordifolia, was investigated for its effects on glucose utilization in skeletal muscle cells, which was followed by determining the anti-hyperglycemic efficacy in our diabetic db/db mice model. We found that tinosporaside augmented glucose uptake by increasing the translocation of GLUT4 to the plasma membrane in L6 myotubes, upon prolonged exposure for 16 h. Moreover, tinosporaside treatment significantly increased the phosphorylation of protein kinase B/AKT (Ser-473) and 5' AMP-activated protein kinase (AMPK, Thr-172). These effects were abolished in the presence of the wortmannin and compound C. Administration of tinosporaside to db/db mice improved glucose tolerance and peripheral insulin sensitivity associated with increased gene expression and phosphorylation of the markers of phosphoinositide 3-kinases (PI3Ks) and AMPK signaling in skeletal muscle tissue. The findings revealed that tinosporaside exerted its antidiabetic efficacy by enhancing the rate of glucose utilization in skeletal muscle, mediated by PI3K- and AMPK-dependent signaling mechanisms.

In vitro and in vivo anti-inflammatory and anti-arthritic effect of Tinospora cordifolia via modulation of JAK/STAT pathway.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disorder causing cartilage and joint degeneration. In spite of the availability of several robust drugs like biologics, most of the patients are unresponsive, and reports of severe adverse effects following long-term use are also there. Subsequently the use of natural plant-based products in RA therapy is broadening over the years. Tinospora cordifolia is a widely used medicinal plant in Ayurveda against various inflammatory disorders including RA. However, there is very limited knowledge regarding the actual molecular events responsible for its therapeutic effect, and this has limited its acceptance among the professionals. PURPOSE: To explore the anti-inflammatory and anti-arthritic effect of hydro-alcoholic extract from Tinospora cordifolia. METHODS: The rich polyphenol nature of the extract was elucidated using HPLC. LPS-stimulated murine macrophage cell line RAW 264.7 was used for in vitro studies, and collagen-induced arthritis (CIA) model was used for in vivo studies. RESULTS: The polyphenols in TCE were identified using HPLC. TCE effectively downregulated the level of pro-inflammatory mediators (IL-6, TNF-α, PGE2, and NO) in LPS-stimulated RAW 264.7 cells. Subsequently the upregulated expression of COX-2 and iNOS following LPS stimulation were also downregulated by TCE. Furthermore, TCE targeted the upstream kinases of the JAK/STAT pathway, a crucial inflammatory pathway. The expression of VEGF, a key angiogenic factor as well as an inflammatory mediator was also decreased following pre-treatment with TCE. The anti-arthritic effect of TCE (150 mg/kg) was evaluated in the CIA model as well. From the results of histopathology, oral administration of TCE was found to be effective in reducing the clinical symptoms of arthritis including paw edema, erythema, and hyperplasia. In vivo results validated the in vitro results and there was a significant reduction in serum level of pro-inflammatory cytokines and mediators (IL-6, TNF-α, IL-17, NO, and PGE2). The phosphorylation of STAT3 and the expression of VEGF were also downregulated following TCE treatment. CONCLUSION: Our study provided a detailed insight into the molecular events associated with anti-inflammatory and anti-arthritic effect of Tinospora cordifolia.

Acute Sleep Deprivation-Induced Anxiety and Disruption of Hypothalamic Cell Survival and Plasticity: A Mechanistic Study of Protection by Butanol Extract of Tinospora cordifolia.

Since sleep is a key homeostatic phenomenon of the body, therefore understanding the complex etiology of the neurological outcome of sleep deprivation (SD) such as anxiety, depression, cognitive dysfunctions, and their management is of utmost importance. The findings of the current study encompass the neurobehavioral as well as hormonal, and neuroinflammatory changes in serum and hypothalamus region of the brain as an outcome of acute SD and their amelioration by pre-treatment with butanol extract of Tinospora cordifolia. SD group animals showed anxiety-like behavior as evident from Elevated Plus Maze data and higher serum cortisol levels, whereas, pre-treatment with B-TCE showed anxiolytic activity and also reduced cortisol levels which was corroborated by an increase in leptin and insulin levels. Further, SD induced elevation of serum pro-inflammatory cytokines IL-6, TNF-α, IL-1ß, and MCP-1 and subsequent activation of astroglial cells in the hypothalamus was suppressed in B-TCE pre-treated animals. The current findings suggest that besides the cortical structures, hypothalamus region's synaptic plasticity and cell survival are adversely impacted by acute SD. Further active ingredients present in B-TCE may be useful for the management of SD-induced anxiety, systemic inflammation, and neuroinflammation by targeting hypothalamic BDNF-TrkB/PI3K-Akt pathways.

Dietary intervention with Tinospora cordifolia improved aging-related decline in locomotor coordination and cerebellar cell survival and plasticity in female rats.

Reduced bone mineral density, and muscle strength are the hallmark of aging-related motor coordination deficits and related neuropathologies. Since cerebellum regulates motor movements and balance perception of our body, therefore it may be an important target to control the age-related progression of motor dysfunctions. Dry stem powder of Tinospora cordifolia (TCP) was tested as a food supplement to elucidate its activity to attenuate age-associated locomotor dysfunctions. Intact acyclic middle-aged female rats were used in this study as the model system of the transition phase from premenopause to menopause in women along with cycling young adult rats. Normal chow or 30% High Fat Diet (HFD), supplemented with or without TCP was fed to animals for 12 weeks and then tested for locomotor performance on rotarod followed by post-sacrifice protein expression studies. In comparison to young adults, middle-aged animals showed an increase in number of falls and lesser time spent in rotarod performance test, whereas, animals given TCP supplemented feed showed improvement in performance with more pronounced effects observed in normal chow than HFD fed middle-aged rats. Further, due to its multicomponent nature TCP was found to target the expression of various markers of neuroinflammation, apoptosis, cell survival, and synaptic plasticity in the cerebellum region. The current findings suggest that TCP supplementation in the diet may prove to be a potential interventional strategy for the management of frailty and fall-associated morbidities caused by aging-related deterioration of bone mineral density, and muscle strength.

Aging-related changes in metabolic indicators in female rats and their management with Tinospora cordifolia.

Conflicting reports of HRT necessitates exploration of therapeutic interventions with the least side effects to preserve metabolic homeodynamics in women later in life. The current study was designed to elucidate the cumulative effects of aging and/or high fat diet (HFD) on some metabolic indicators and their management by Tinospora cordifolia stem powder (TCP) using middle-aged acyclic and young adult cyclic female rats as the model system. Animals were fed on either normal chow or HFD supplemented with or without TCP. Blood and liver tissue were collected for biochemical, and histological studies as well as for expression of proteins regulating lipid metabolism. Animals fed with TCP supplemented normal chow feed showed bodyweight management over 12-weeks despite their high feed and calories intake compared to young and age-matched controls as well as HFD-fed animals. TCP dose used was not toxic and rather prevented age-associated liver dysfunctions and ameliorated dyslipidemia and oxidative stress, normalized blood glucose, insulin, leptin, and secretary pro-inflammatory cytokines. Further, bodyweight management effect of TCP was observed to target AMPK signalling pathway as the mediator of lipogenesis, sterol biosynthesis, lipolysis, and ß-oxidation of fatty acids. These findings suggest that TCP supplementation in diet may be a potential interventional strategy to ameliorate aging-associated hepatic and metabolic dysfunctions and to promote healthy aging.