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.

N-Methylneolitsine as a new and potent acetylcholinesterase inhibitor of Cissampelos pareira Linn. aerial parts: bioassay-guided isolation and quantitative densitometric analysis.

The rising geriatric population is expected to increase the demand for drugs treating neurodegenerative diseases. The present work is aimed to discover acetylcholinesterase (AChE) inhibitors from Cissampelos pareira Linn. aerial parts (Family: Menispermaceae). Bioassay-guided isolation, AChE inhibition study and estimation of the therapeutic marker in different parts of raw herbs were conducted. The structure of the compound (1) was elucidated as N-methylneolitsine by using NMR (1D and 2D) and ESI-MS/MS spectral data, which is a new natural analogue of neolitsine. It showed good AChE inhibition with an IC50 value of 12.32 µg/mL. It was densitometrically estimated to be 0.074 - 0.33% in aerial parts of C. pareira, collected from various locations. The alkaloid reported here could be potentially useful for the treatment of various neurodegenerative diseases and the aerial part of C. pareira could be used as a promising ingredient for various preparations treating neurodegenerative diseases.

Immunoprotective potential of Ayurvedic herb Kalmegh (Andrographis paniculata) against respiratory viral infections - LC-MS/MS and network pharmacology analysis.

INTRODUCTION: Immunity boosting has emerged as a global strategy to fight the SARS-CoV-2 pandemic situation. In India, AYUSH systems of medicine have been promoted as an immune-protection strategy. Andrographis paniculata (Burm. F) Nees (AP) mentioned in Ayurveda has been widely used for treating sore throat, flu, and upper respiratory tract infections which may provide possible novel therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways. OBJECTIVES: The present work uses liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics and combination synergy analysis based on network pharmacology to mine multimode evidence to understand the possible mechanism of action, diseases association, protein-protein interaction and major pathways involved therein. MATERIAL AND METHODS: Metabolite profiling was performed by Agilent QTOF LC-MS/MS system. Network pharmacology analysis was performed by using functional annotation analysis based on databases like Binding DB, STRING, DAVID and KEGG for further data mining. Further combination synergy was evaluated using "neighbourhood approach" and networks were constructed through Cytoscape 3.2.1. RESULTS: The molecules from kalmegh provides immune-protection and anti-viral response via involving different pathways, like toll-like receptor pathway, PI3/AKT pathway and MAP kinase pathways against COVID-19 infection. The KEGG analysis showed that in a vast majority of the most enriched pathways, AP were associated with viral infections and upper respiratory tract infections. CONCLUSIONS: The results suggest a synergy between andrographolide and other molecules identified as safe and efficacious anti-inflammatory agent having effects on upper respiratory tract infections and can significantly decrease the production of cytokines and pro-inflammatory factors in viral infections.

Estimation of Levodopa in the Unani Drug Mucuna pruriens Bak. and Its Marketed Formulation by High-Performance Thin-Layer Chromatographic Technique.

BACKGROUND: Mucuna pruriens Bak. Syn. Mucuna prurita Hook. seed is the rich source of levodopa (L-dopa) and has been used in traditional medicines to treat diseases resembling Parkinson's disease. OBJECTIVE: In the present study, a new HPTLC method was developed and validated for estimation of L-dopa from M. pruriens (black- and white-colored seeds) collected from two different locations in India. METHOD: TLC aluminum plates precoated with silica gel were used as the stationary phase. The plates were developed to a distance of 60 mm at a temperature of 22 ± 4°C in a twin glass chamber saturated with ethyl acetate-methanol-formic acid-water (15+3+3+4.5, v/v/v/v), as the mobile phase. RESULTS: The Rf value of L-dopa was found to be 0.45. L-dopa was quantified at 282 nm, the wavelength of maximum absorbance by a densitometric scanner. The TLC plate was derivatized by ninhydrin reagent and photodocumented. L-dopa showed a good linearity in the concentration range 400-1000 ng/spot. The linear regression analysis of calibration plot showed good linear relationship between peak area and peak height (r2 = 0.997). CONCLUSIONS: The method was validated for precision, repeatability, and accuracy. Recovery was determined by spiking L-dopa with samples and was found to be 96.10%. HIGHLIGHTS: L-dopa was found to be present at concentration 3.02-4.72% in samples and its formulation.

RP-HPLC and HPTLC Methods for Analysis of Selected Herbs Used as Complexion Promoters in Ayurveda and Unani Systems of Medicine.

BACKGROUND: In Ayurvedic and Unani texts, many herbs and formulations are mentioned as complexion promoters having skin brightening and whitening effects that downregulate melanin synthesis. However, with the assistance of chromatographic techniques, further validation of scientific standardization is required. OBJECTIVE: To validate individual herbs and formulations in the ancient literature, some scientific aspects are to be focused on, including standardization of herbs or herbal products consisting of the active compounds. METHODS: Out of many herbs having complexion promoting properties, three herbs (Myristica fragrans, Hemidesmus indicus, and Inula racemosa) were selected for the study. In the present study, validated reverse phase (RP)-HPLC and high-performance TLC (HPTLC) methods were developed for standardization of the herbs. RESULTS: It was observed that the quercetin present in M. fragrans was 0.62% (w/w) with a retention time (Rt) of 6.23 min, the ferulic acid present in H. indicus was 1.39% (w/w) with an Rt of 8.083 min, and the chlorogenic acid present in I. racemosa was 1.03% (w/w) with an Rt of 3.19 min. The HPTLC method showed 1.23% (w/w) of quercetin present in M. fragrans with a retardation factor (Rf) of 0.48, ferulic acid in H. indicus was 1.52% (w/w) with an Rf of 0.44, and chlorogenic acid was 1.09% (w/w) in I. racemosa with an Rf of 0.52. CONCLUSIONS: This specific and precise validated method can be useful for the quality evaluation and quantitative determination of the constituents in complexion-promoting herbs from Ayurveda and Unani systems of medicine. HIGHLIGHTS: The exploration of complexion promoters from Ayurveda and Unani; quality evaluation of complexion promoters herbs from Ayurveda and Unani; HPTLC and RP-HPLC analysis of herbal extracts used and their validation.

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.

Boswellia serrata extract attenuates inflammatory mediators and oxidative stress in collagen induced arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease which leads to destruction of joints. Current treatment modalities for RA either produce symptomatic relief (NSAIDs) or modify the disease process (DMARDs). Though effective, their use is also limited by their side effects. As a result, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. Our aim was to evaluate the antioxidant and antiarthritic activity of Boswellia serrata gum resin extract (BSE) in collagen induced arthritis. Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. BSE was administered at doses of 100 and 200mg/kg body weight once daily for 21 days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, catalase, SOD and NO), inflammatory mediators (IL-1ß, IL-6, TNF-α, IL-10, IFN-γ and PGE2), and histological studies in joints. BSE was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, catalase, SOD and NO) studied. Oral administration of BSE resulted in significantly reduced levels of inflammatory mediators (IL-1ß, IL-6, TNF-α, IFN-γ and PGE2), and increased level of IL-10. The protective effects of BSE against RA were also evident from the decrease in arthritis scoring and bone histology. The abilities to inhibit proinflammatory cytokines and modulation of antioxidant status suggest that the protective effect of Boswellia serrata extract on arthritis in rats might be mediated via the modulation of immune system.

Piperine ameliorates oxidative stress, inflammation and histological outcome in collagen induced arthritis.

OBJECTIVES: Piperine, a main component of Piper species, is a plant alkaloid with a long history of medical use in a variety of inflammatory disorders like rheumatoid arthritis. Due to side effects in current treatment modalities of rheumatoid arthritis, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. The aim of this work was to evaluate the anti-inflammatory and antiarthritic effects of piperine. METHODS: Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. Piperine was administered at a dose of 100mgkg(-1) and indomethacin at 1mgkg(-1) body weight once daily for 21days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO), inflammatory mediators (IL-1ß, TNF-α, IL-10 and PGE2) and histological studies in joints. RESULTS: Piperine was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO) studied. Oral administration of piperine resulted in significantly reduced the levels of pro-inflammatory mediators (IL-1ß, TNF-α and PGE2) and increased level of IL-10. The protective effects of piperine against RA were also evident from the decrease in arthritis scoring and bone histology. CONCLUSIONS: In conclusion, the fact that piperine alter a number of factors known to be involved in RA pathogenesis indicates that piperine can be used similar to indomethacin as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis.

Hesperidin inhibits collagen-induced arthritis possibly through suppression of free radical load and reduction in neutrophil activation and infiltration.

Rheumatoid arthritis is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone in a chronic phase. Pathology of rheumatoid arthritis suggests autoimmunity linked to inflammation. In our study, rheumatoid arthritis was induced in Wistar rats by intradermal injections of 100 µl of emulsion containing bovine type II collagen in complete Freund's adjuvant at the base of the tail. Disease developed about 13 ± 1 days after immunization and treatment with hesperidin (HES) at a dose of 160 mg kg(-1) body weight was given after onset of disease daily until 20th day. The effect of treatment in the rats was monitored by clinical scoring, biochemical parameters and histological evaluations in joints. A steady increase in the articular elastase, nitric oxide and lipid peroxidation was observed in joints of arthritic rats as compared to control, whereas a significant decrease in reduced glutathione, superoxide dismutase activity and catalase was observed in collagen-induced arthritis rats as compared to control group. The results from the present work indicate that the treatment with hesperidin was effective in bringing about significant changes on all the parameters studied in collagen-induced arthritis rats. These data confirm that erosive destruction of the joint cartilage in collagen-induced arthritis is due free radicals released by activated neutrophils and produced by other biochemical pathways. In the present study, an attempt has been made to amelioration of the disease process by a natural product. These results suggest that oral administration of HES could be effective for treating human RA patients.

Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats.

Thymoquinone (TQ) is the major active compound derived from Nigella sativa. Our aim of this work was to evaluate the antioxidant and antiarthritic activity of TQ in Wistar rat by collagen induced arthritis (CIA). TQ was administered at a dose of 5mgkg(-1) body weight once daily for 21days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, catalase, SOD and NO), inflammatory mediators (IL-1ß, IL-6, TNF-α, IL-10, IFN-γ and PGE(2)) and histological studies in joints. TQ was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, catalase, SOD and NO) studied. Oral administration of TQ resulted in significantly reduced the levels of pro-inflammatory mediators (IL-1ß, IL-6, TNF-α, IFN-γ and PGE(2)) and increased level of IL-10. The protective effects of TQ against RA were also evident from the decrease in arthritis scoring and bone histology. In conclusion, the fact that TQ abolished a number of factors known to be involved in RA pathogenesis indicates that the administration of thymoquinone may have potential value in the treatment of inflammatory disease.

Insulinomimetic activity of two new gallotannins from the fruits of Capparis moonii.

Bioassay guided fractionation of the hydro-alcoholic extract of the fruits of Capparis moonii, led to the isolation of two new chebulinic acid derivatives. The compounds 1 and 2 displayed significant glucose uptake effect of 223% and 219% over the control at the 10ng/ml and 100ng/ml concentration, respectively. The increased glucose uptake effects of the compounds were associated with significant IR and IRS-1 phosphorylation, GLUT4 and PI3-kinase mRNA expression in the L6 cells.

Validated HPLC-UV method for the determination of berberine in raw herb Daruharidra (Berberis aristata DC), its extract, and in commercially marketed Ayurvedic dosage forms.

A new, simple, sensitive, selective, and precise high-performance liquid chromatography (HPLC) method for analysis of berberine in crude plant material, herbal extract, and ayurvedic dosage forms was developed and validated. The stationary phase was inert sil C(18) column The mobile phase consisting of acetonitrile (HPLC Grade) and potassium dihydrogen phosphate buffer (pH 2.5) in a gradient flow was used.The column was equilibrated with the mobile phase (flow rate 1.0 ml/min); elution was monitored at 346 nm. The linear regression analysis data for the calibration plots showed good linear relationship, with r(2)= 0.9942 in the concentration range of 16380-30420 µg/ml with respect to the peak area. The method was validated for specificity, precision, recovery, and linearity according to the International Conference on Harmonization guidelines. Statistical analysis of the data showed that the method is reproducible and selective for the estimation of berberine.

The effect of water activity and storage temperature on the growth of Aspergillus flavus in medicinal herbs.

The quality control of medicinal herbs post harvesting or after collection becomes very critical because of susceptibility to fungal invasion during storage depending on the temperature and humidity of the storage area. The information on moisture equilibrium is important on the process and storage of foods which can be extended to medicinal herbs. In the present study, the growth of Aspergillus flavus was observed on selected ten medicinal herbs with water activity aw above 0.81 when stored at 25 +/- 2 degrees C, 30 +/- 2 degrees C and 40 +/- 2 degrees C except for Picrorhiza kurrooa and Alpinia galanga which were found to have anti-fungal properties. Aspergillus flavus did not grow in any samples of medicinal herbs with water activity aw below 0.81 at temperatures of 25 +/- 2 degrees C, 30 +/- 2 degrees C and 40 +/- 2 degrees C. Also Aspergillus flavus did not grow in any samples of medicinal herbs with water activity aw above 0.81 when stored below 10 +/- 2 degrees C. Therefore it can be concluded that the contamination of medicinal herbs with aflatoxins can be minimized by controlling water activity and storage temperature. Sorption isotherms (desorption) can be interpreted to determine the optimum drying which can lower the water activity to the level required for preventing growth of Aspergillus flavus and also for ensuring quality of medicinal herbs which may get destroyed upon over drying. Furthermore, it also saves incremental cost in prolonged drying over the optimum drying.