Ursolic Acid Restores Redox Homeostasis and Pro-inflammatory Cytokine Production in Denervation-Induced Skeletal Muscle Atrophy.

Skeletal muscle (SkM) atrophy results from metabolic disorders causing body and muscle mass loss, affecting morbidity and mortality. Increased oxidative stress, inflammation, and poor prognosis are the leading causes of involuntary weight loss. Ursolic acid (UA), known for its antioxidant and anti-inflammatory properties, can potentially reduce oxidative stress and inflammation in muscles, but its effects on muscle mass regulation are still unknown.

Skeletal muscle atrophy after sciatic nerve damage: Mechanistic insights.

Sciatic nerve injury leads to molecular events that cause muscular dysfunction advancement in atrophic conditions. Nerve damage renders muscles permanently relaxed which elevates intracellular resting Ca levels. Increased Ca levels are associated with several cellular signaling pathways including AMPK, cGMP, PLC-β, CERB, and calcineurin.

Integrated omics analysis revealed the intervention modulated multiple signaling pathways in hypertriglyceridemia patients-a pilot clinical trial.

Purpose: Hypertriglyceridemia (HTG) is strongly associated with the various types of disease conditions and evolving as epidemics. Hence, it is important to identify molecules that lower the triglyceride and chylomicron levels. is an illustrious Ayurveda drug, has proved juvenile and immunomodulatory properties.

Natural products: Potential therapeutic agents to prevent skeletal muscle atrophy.

The skeletal muscle (SkM) is the largest organ, which plays a vital role in controlling musculature, locomotion, body heat regulation, physical strength, and metabolism of the body. A sedentary lifestyle, aging, cachexia, denervation, immobilization, etc. Can lead to an imbalance between protein synthesis and degradation, which is further responsible for SkM atrophy (SmA).

Dynamics and Interplay between Autophagy and Ubiquitin-proteasome system Coordination in Skeletal Muscle Atrophy.

Skeletal muscles are considered the largest reservoirs of the protein pool in the body and are critical for the maintenances of body homeostasis. Skeletal muscle atrophy is supported by various physiopathological conditions that lead to loss of muscle mass and contractile capacity of the skeletal muscle. Lysosomal mediated autophagy and ubiquitin-proteasomal system (UPS) concede the major intracellular systems of muscle protein degradation that result in the loss of mass and strength.

The dependency of autophagy and ubiquitin proteasome system during skeletal muscle atrophy.

Among the four proteolytic systems in the cell, autophagy and the ubiquitin-proteasome system (UPS) are the main proteolytic events that allow for the removal of cell debris and proteins to maintain cellular homeostasis. Previous studies have revealed that these systems perform their functions independently of each other. However, recent studies indicate the existence of regulatory interactions between these proteolytic systems via ubiquitinated tags and a reciprocal regulation mechanism with several crosstalk points.

Dynamics of Toll-like Receptors Signaling in Skeletal Muscle Atrophy.

Skeletal muscle atrophy has been characterized as a state of uncontrolled inflammation and oxidative stress that escalates protein catabolism. Recent advancement supports impinging signaling molecules in the muscle fibers controlled through toll-like receptors (TLR). Activated TLR signaling pathways have been identified as inhibitors of muscle mass and provoke the settings for muscle atrophy.

Intervention of Ayurvedic drug attenuates the metabolic alterations in hypertriglyceridemia: a pilot clinical trial.

Purpose: Hypertriglyceridemia (HG) is an independent risk factor with more prevalence than hypercholesterolemia and its attributes to cardiovascular disease (CVD) and pancreatitis. Hence, it becomes imperative to search for new triglyceride (TG) lowering agents. (TC) is a well-known Ayurvedic drug and a rich source of protoberberine alkaloids hence can contribute to TG lowering without side effects.

Magnoflorine prevent the skeletal muscle atrophy via Akt/mTOR/FoxO signal pathway and increase slow-MyHC production in streptozotocin-induced diabetic rats.

Ethnopharmacological Relevance: Tinospora cordifolia (TC) is being used as a blood purifier in Ayurveda since ancient time. It is a very popular immunomodulator and holds anti-inflammatory and anti-oxidative potential, hence anti-aging properties. Therefore, it is also known as 'Amrita' in Ayurveda and is widely used to treat diabetes mellitus type II (T2DM) and its secondary complications; however, its underlying mechanism was not expedited to date.

S-allyl cysteine: A potential compound against skeletal muscle atrophy.

Background: Oxidative stress is crucial player in skeletal muscle atrophy pathogenesis. S-allyl cysteine (SAC), an organosulfur compound of Allium sativum, possesses broad-spectrum properties including immuno- and redox-modulatory impact. Considering the role of SAC in regulating redox balance, we hypothesize that SAC may have a protective role in oxidative-stress induced atrophy.

Tinospora cordifolia protects from skeletal muscle atrophy by alleviating oxidative stress and inflammation induced by sciatic denervation.

Ethanopharmacological Relevance: Tinospora cordifolia (TC) is widely being used as immunomodulatory and re-juvenile drug and well described in Indian Ayurveda system of medicine. Rejuvenation also means the fine tuning of the skeletal muscles. Skeletal muscle related disorder, i.

Interactions of a medicinal climber Tinospora cordifolia with supportive interspecific plants trigger the modulation in its secondary metabolic profiles.

Tinospora cordifolia (TC) is scientifically proven immunomodulatory drug being used for centuries. Ancient literature reported that inter-specific interactions change medicinal properties of TC. Thus, the current study is aimed to understand the influence of interspecific biotic interactions on chemo-profiles of TC.

Role of Pro-inflammatory Cytokines in Regulation of Skeletal Muscle Metabolism: A Systematic Review.

Background: Metabolic pathways perturbations lead to skeletal muscular atrophy in the cachexia and sarcopenia due to increased catabolism. Pro-inflammatory cytokines induce the catabolic pathways that impair the muscle integrity and function. Hence, this review primarily concentrates on the effects of pro-inflammatory cytokines in regulation of skeletal muscle metabolism.

Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties.

The article describes the use of facile one-pot, high-yielding reactions to synthesize substituted 3,4-dimethyl-1-pyrrole-2-carboxamides - and carbohydrazide analogues - as potential antifungal and antimicrobial agents. The structural identity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity.

Non-invasive Qualitative Urinary Metabolomic Profiling Discriminates Gut Microbiota Derived Metabolites in the Moderate and Chronic Alcoholic Cohorts.

Background: Excessive alcohol consumption damages the intestine and liver cells directly as well as through unbalancing the gut microbiota.

Objective: The current study was undertaken to correlate the alcohol consumption and change in urinary metabolites profile linked with gut microbiota.

Method: Non-alcoholic (control) healthy (n=22) and moderate alcoholic (n=26) males with an average age of 39.

Protective Effect of Hydroxytyrosol Against Oxidative Stress Mediated by Arsenic-Induced Neurotoxicity in Rats.

The present study reports beneficial effect of hydroxytyrosol (HT) against arsenic (As)-induced oxidative stress in the rat brain. Rats were orally administered with sodium arsenite dissolved in distilled water (25 ppm, by oral gavage) for 8 weeks or HT (10 mg/kg b. wt.

Plasma metabolomics reveal the correlation of metabolic pathways and Prakritis of humans.

Background: Ayurveda, an ancient Indian medicinal system, has categorized human body constitutions in three broad constitutional types (prakritis) i.e. Vata, Pitta and Kapha.

Antimicrobial metabolites from Saraca asoca impairs the membrane transport system and quorum-sensing system in Pseudomonas aeruginosa.

This study was conducted to explore the antimicrobial mechanism of metabolites from Saraca asoca (SA1) using differential proteomics and metabolic profile of Pseudomonas aeruginosa after treatment with effective sub-MIC dose of 312 µg/mL. SA1 fraction was found to contain antibacterial metabolites catechol, protocatechuic acid, and epigallocatechin gallate. Proteome analysis revealed 33 differentially expressed proteins after SA1 treatment.

Guduchi Sawras (Tinospora cordifolia): An Ayurvedic drug treatment modulates the impaired lipid metabolism in alcoholics through dopaminergic neurotransmission and anti-oxidant defense system.

Tinospora cordifolia (Guduchi Sawras) though has been clearly demonstrated in literature for its hypolipidemic and anti-alcoholism properties but its anti-hyperlipidemia mechanistic approach is still missing. Moreover, its direct implication with alcohol induced hyperlipidemia has also not been reported till date. In order to explore the answers of these questions, phytochemicals of Tinospora cordifolia water extract "Guduchi Sawras" (GS) was analyzed using HPLC-Q-TOF-MS.

Efficacy and risk profile of anti-diabetic therapies: Conventional vs traditional drugs-A mechanistic revisit to understand their mode of action.

An increasing array of anti-diabetic drugs are available today, yet Type-2 diabetes mellitus (T2DM) - remains a life threatening disease, causing high mortality and morbidity in developing and developed countries. As of now, no effective therapy is available for the complete eradication/cure of diabetes and its associated complications. Therefore, it is time to re-think and revisit molecular pathways and targets of each existing drug in order to identify multiple targets from different signaling pathways that may be manipulated simultaneously to treat or manage T2DM effectively.

Coumarin Derivatives as Adjuvants: From In Silico Physicochemical Characterization to In Vitro Evaluation against Gram Positive Bacteria.

Aims: A series of acylated coumarin derivatives have been evaluated for their in silico ADMET properties and in vitro antibacterial activities.

Methods And Results: In silico analysis confirmed their physicochemical properties in conformation with various layout filters and further their ADMET properties were predicted. Antibacterial activities were evaluated by Resazurin based microbroth dilution assay against standard Gram positive bacteria: Staphylococcus aureus (MTCC No.

Detection and qualitative analysis of fatty acid amides in the urine of alcoholics using HPLC-QTOF-MS.

Fatty acid amides (FAAs) in alcoholism lead to liver diseases. These amides have been reported in plasma and in other organs of the body, while their detection or presence in the urine is still unknown. Therefore, the focus of the current study was to detect and analyze FAAs qualitatively in urine samples of alcoholics.

Moderate alcohol consumption in chronic form enhances the synthesis of cholesterol and C-21 steroid hormones, while treatment with Tinospora cordifolia modulate these events in men.

Chronic and heavy alcohol consumption disrupts lipid metabolism and hormonal balance including testosterone levels. However, studies doubt the relationship between moderate alcohol intake and sex hormone levels. Therefore, the aim of the present investigation was to establish the direct impact of chronic and moderate alcohol intake on cholesterol homeostasis and steroid hormone synthesis.

Protective Effects of Tinospora cordifolia on Hepatic and Gastrointestinal Toxicity Induced by Chronic and Moderate Alcoholism.

Aims: Heavy alcohol intake depletes the plasma vitamins due to hepatotoxicity and decreased intestinal absorption. However, moderate alcohol intake is often thought to be healthy. Therefore, effects of chronic moderate alcohol intake on liver and intestine were studied using urinary vitamin levels.

Skeletal muscle atrophy: Potential therapeutic agents and their mechanisms of action.

Over the last two decades, new insights into the etiology of skeletal muscle wasting/atrophy under diverse clinical settings including denervation, AIDS, cancer, diabetes, and chronic heart failure have been reported in the literature. However, the treatment of skeletal muscle wasting remains an unresolved challenge to this day. About nineteen potential drugs that can regulate loss of muscle mass have been reported in the literature.