Diabetes mellitus and Alzheimer's disease: Understanding disease mechanisms, their correlation, and promising dual activity of selected herbs.

ETHNOPHARMACOLOGICAL RELEVANCE: This review explores the link between Type 2 Diabetes Mellitus (T2DM) and diabetes-induced Alzheimer's disease (AD). It emphasizes the shared pathophysiological links and mechanisms between the two conditions, focusing on reduced insulin levels and receptors, impaired glucose metabolism, insulin resistance, mitochondrial dysfunction, and oxidative damage in AD-affected brains-paralleling aspects of T2DM. The review suggests AD as a "diabetes of the brain," supported by cognitive enhancement through antidiabetic interventions. It focuses on the traditionally used Indian herbs as a means to manage both conditions while addressing developmental challenges. AIM OF THE STUDY: This study explores the DM-AD connection, reviewing medicinal herbs with protective potential for both ailments, considering traditional uses and developmental challenges. MATERIALS AND METHODS: Studied research, reviews, and ethnobotanical and scientific data from electronic databases and traditional books. RESULTS: The study analyzes the pathophysiological links between DM and AD, emphasizing their interconnected factors. Eight Ayurvedic plants with dual protective effects against T2DM and AD are thoroughly reviewed with preclinical/clinical evidence. Historical context, phytoconstituents, and traditional applications are explored. Innovative formulations using these plants are examined. Challenges stemming from phytoconstituents' physicochemical properties are highlighted, prompting novel formulation development, including nanotechnology-based delivery systems. The study uncovers obstacles in formulating treatments for these diseases. CONCLUSION: The review showcases the dual potential of chosen medicinal herbs against both diseases, along with their traditional applications, endorsing their use. It addresses formulation obstacles, proposing innovative delivery technologies for herbal therapies, while acknowledging their constraints. The review suggests the need for heightened investment and research in this area.

Comprehensive insights into rheumatoid arthritis: Pathophysiology, current therapies and herbal alternatives for effective disease management.

Rheumatoid arthritis is a chronic autoimmune inflammatory disease characterized by immune response overexpression, causing pain and swelling in the synovial joints. This condition is caused by auto-reactive antibodies that attack self-antigens due to their incapacity to distinguish between self and foreign molecules. Dysregulated activity within numerous signalling and immunological pathways supports the disease's development and progression, elevating its complexity. While current treatments provide some alleviation, their effectiveness is accompanied by a variety of adverse effects that are inherent in conventional medications. As a result, there is a deep-rooted necessity to investigate alternate therapeutic strategies capable of neutralizing these disadvantages. Medicinal herbs display a variety of potent bioactive phytochemicals that are effective in the complementary management of disease, thus generating an enormous potency for the researchers to delve deep into the development of novel phytomedicine against autoimmune diseases, although additional evidence and understanding are required in terms of their efficacy and pharmacodynamic mechanisms. This literature-based review highlights the dysregulation of immune tolerance in rheumatoid arthritis, analyses the pathophysiology, elucidates relevant signalling pathways involved, evaluates present and future therapy options and underscores the therapeutic attributes of a diverse array of medicinal herbs in addressing this severe disease.

Microparticulate and nanotechnology mediated drug delivery system for the delivery of herbal extracts.

There has been a growing interest in the scientific community to explore the complete potential of phytoconstituents, herbal or plant-based ingredients owing to a range of benefits they bring along. The herbal plants accommodate many phytoconstituents that are responsible for various activities such as anti-oxidant, antimicrobial, anticancer, anti-inflammatory, anti-allergic, hepatoprotective, etc. However, these phytoconstituents are highly sensitive to several environmental and physiological factors such as pH, oxygen, heat, temperature, humidity, stomach acid, enzymes, and light. Hence, there is need for the development of a drug delivery system that can protect the phytoconstituents from both internal and external conditions. In this regard, a microparticulate drug delivery system is considered amongst the ideal choice owing to its small size, ability to protect the environment-sensitive active constituents, in achieving sustained drug delivery, targeted drug delivery, protection of the drug from physiological conditions, minimizing drug-related side effects, etc.

A novel UPLC-MS/MS method for simultaneous quantification of trigonelline, 4-hydroxyisoleucine, and diosgenin from Trigonella foenum-graecum extract: Application to pharmacokinetic study in healthy and type 2 diabetic rats.

Trigonelline (TR), 4-hydroxyisoleucine (4-HI), and diosgenin (DG) are the main bioactives of the purified standardized extract of the popular plant Trigonella foenum-graecum L. (TFG), and it has been proven effective for the treatment of various diseases. However, to the best of our knowledge, no study has investigated the pharmacokinetic parameters of purified standardized T. foenum-graecum extract in normal and diabetic Wistar rats. The present study has developed and validated a rapid, reliable, and sensitive simultaneous ultra-performance liquid chromatography MS method to estimate these bioactives. The chromatographic separation was achieved using methanol, acetonitrile, and 0.1% formic acid with the ideal gradient flow system on a BEH Shield RP 18 column. A positive electrospray ionization mode was selected to estimate m/z values of TR (138.14 > 94.63), 4-HI (148.19 > 74.08), and DG (415.54 > 271.33). The method was robust and reproducible over the linearity range of 60-5000, 6-5000, and 15-5000 ng/mL for TR, 4-HI, and DG, respectively. Using this novel validated method, we investigated the pharmacokinetic parameters of bioactives using Phoenix WinNonlin version 8.0 (Certera) in normal and diabetic rats. The assay was successfully applied for the estimation of pharmacokinetic parameters using noncompartmental analysis. This investigation shows that the absorption rate increased, whereas distribution and elimination processes slowed down in diabetic rats compared with normal rats.

Evaluation of subacute toxicity and herb-drug interaction potential of an herbal Arishta formulation.

Background Arishta technology is an age-old heritage and uses herbal decoctions to prepare self-generated alcoholic medicines. In Ayurveda, Arishta preparations are widely used as a remedy for metabolic disorders. However, their safety and influence on herb metabolism pathways were not yet explored. Aim: To study the subacute toxicity of a polyherbal Arishta formulation (coded as DB-07) in rats and to evaluate its potential for inhibition of the drug-metabolizing enzyme (Cytochrome P450 3A4). Methodology Experimentally naive rats were treated with graded oral doses of DB-07 (10 and 20 mL/kg/day) for 28 days. During the course of the experiment, all the animals were closely observed for apparent behavioural abnormalities and mortalities. Tissue histology was performed to assess any sign of toxicity. In addition, in vitro CYP3A4 inhibition assay was performed to study the effect on drug metabolism pathways. Results Animals did not show any change in body weight, organ toxicity and food consumption throughout the dosing period of 28 days. Pathophysiological, behavioural status and locomotor activity were not altered. DB-07 did not inhibit CYP3A4 enzyme and drug metabolism pathway in-vitro. Gallic acid and quercetin were identified as phytomarker from the formulation that may be responsible for its activity related safety issue. Conclusion These results indicate that use of DB-07 may be safe with no sign of toxicity for up to 28 days in rats. Further, CYP3A4 inhibition assay indicated that DB-07 is less likely to have herb-drug interactions when concomitantly administered with CYP3A4 inhibitors or inducer.

Evaluation of herb-drug interaction of a polyherbal Ayurvedic formulation through high throughput cytochrome P450 enzyme inhibition assay.

ETHNOPHARMACOLOGICAL RELEVANCE: Arishtas are Ayurvedic formulation made with decoction of herbs. Arjunarishta formulation is being used in Ayurveda for cardio-protective activity. Ashwagandharishta formulation possesses antioxidant, anti-atherosclerotic and anti-stress properties. Ridayarishta, a novel empirical formulation was prepared using combination of selected ingredients from these two formulations to support healthy heart functions and to reduce stress. AIM OF THE STUDY: Aim of the Study was to investigate herb-drug interaction (HDI) of Ridayarishta formulation through human hepatic cytochrome P450 (CYP450) enzyme inhibition assay. MATERIALS AND METHODS: Ridayarishta formulation was phyto-chemically standardized against arjunolic acid, arjunetin, berberine, piperine, resveratrol and withaferin-A using high performance thin layer chromatography (HPTLC) analysis. The formulation was standardized with respect to ethanol by gas chromatographic (GC) analysis. HDI was evaluated with Ridayarishta formulation and amlodipine besilate, atenolol, atorvastatin, metformin, glipizide glimepiride cocktail using high throughput CYP450 enzyme inhibition assay; against CYP1A2, 2C19, 2D6 and 3A4 isozymes. RESULTS: Contents of arjunolic acid, arjunetin, berberine, piperine, resveratrol and withaferin-A in Ridayarishta formulation were found to be 1.76±0.12, 1.51±0.09, 1.85±0.05, 3.2±0.12, 1.21±0.08, and 2.16±0.09ppm, respectively. Quantity of ethanol in Ridayarishta was found to be 7.95±0.023% (V/V). Ridayarishta showed significantly higher (P<0.001) IC50 value against CYP1A2 (IC50-13.80±1.96µg/mL), 2C19 (IC50-14.343±2.28µg/mL), 2D6 (IC50-0.897±0.28µg/mL) and 3A4 (IC50-32.057±2.51µg/mL) compared to positive controls such as furafylline, tranylcypromine, quinidine and ketoconazole respectively. Cocktail of herbal formulation and cardio protective, antihypertensive, anti-diabetic drugs showed significantly (P<0.001and P<0.01) less or negligible HDI. CONCLUSION: Ridayarishta formulation alone and cocktail with amlodipine besilate, atenolol, atorvastatin, metformin, glipizide, glimepiride had negligible or insignificant effect on CYP450 inhibition. It may be concluded that consumption of Ridayarishta along with selective cardio protective, antihypertensive and anti-diabetic conventional medicine is safe with negligible or without any significant CYP450 (CYP1A2, 2C19, 2D6 and 3A4) inhibition mediated HDI.