Bidirectional Effect of Triphala on Modulating Gut-Brain Axis to Improve Cognition in the Murine Model of Alzheimer's Disease.

SCOPE: The emerging role of gut microbiota and their metabolites in the modulation of the gut-brain axis has received much attention as a new hope for the treatment of hard-to-treat chronic neurodegenerative diseases like Alzheimer's disease. The naturally occurring polyphenols can restore the gut-brain axis by modulating gut microbiota and brain neurotransmitters. The Indian traditional medicine Triphala, a rich source of polyphenols, has been used on humans based on Prakriti or disease conditions for many years. METHODS AND RESULTS: In this study, the dual mode (morning and evening) action of Triphala is used to provide scientific evidence of its superior preventive and therapeutic efficacy in C57BL/6 and 5xFAD, APP/PS1 transgenic mouse model of Alzheimer's disease. The study observes that Triphala treatment has significantly improved cognitive function, by modulating the APP pathway, reducing inflammation, and restoring the gut-brain axis by increasing the gut microbiota phyla of Bacteroides, Proteobacteria, Actinobacteria, etc., involved in maintaining the gut homeostasis. CONCLUSIONS: The study paves a new path for using dual modes of Triphala alone or in combination to treat incurable AD.

Taurine deficiency as a driver of aging.

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

Elucidating the antifungal activity and mechanism of action of bioactive phytochemicals against fungal dermatitis isolates.

Dermatophytosis has been the most common cause of superficial fungal infections which invade the keratinized tissues of body such as nail, hair, and skin, respectively. Although these infections are treatable and many commercial drugs are available that can be applied topically (clotrimazole, fluconazole, itraconazole, miconazole, voriconazole) on the infected areas but they have very low efficacy and has high probability of relapse. To increase the efficacy of treatment, the patient receives supplementary oral medicines for prolong duration that leads to hepatotoxicity. Previously, it has been reported that some wild medicinal plants possess antifungal capacity due to the presence of bioactive molecules. In present study, these phytochemicals (viz. tannins, saponins, alkaloids, flavonoids) derived from three test plants [Acacia nilotica (babul), Catharanthus roseus (sadabahar) and Ricinus communis (Arandi)] are used as sources of direct medicinal agents to develop an antidermatophytic drug formulation against the clinical fungal isolates associated with affected population. The mechanism of their antifungal potential of partially purified phytochemicals were analyzed using agar well diffusion method, food inhibition assessment and DNA cleavage analysis. The data revealed that the alkaloids are the most potent component possessing antifungal property that is recommended to be used to formulate topical ointment for the dermatophytic infection after competent regulatory approvals. This can be used as promising source of alternative treatment approach and as a competent substitute for chemically synthesized hepatotoxic drugs that are available in market.

Protective manifestation of herbonanoceuticals as antifungals: A possible drug candidate for dermatophytic infection.

Background and Aims: Fungal dermatophytosis or Tinea is a predominance in about 20%-25% of all total world populations. Dermatophyte infections are mainly caused by fungi belonging to Trichophyton, Epidermophyton, and Microsporum genera along with some other fungi. This epidemiological distribution may change with migration, lifestyle, immunosuppressive state, drug therapy, and socioeconomic conditions. Methods: The present review indicated the bioefficacy of herbal and herbonanoconjugate as safe management of fungal dermatophytic infection. Results: It also emphasized the action mechanism as fungicidal and fungistatic with different harmful impacts indicating the need for alternative therapeutics. Simultaneously, the herbal and herbonanoconjugate approaches proved better to manage the prevalence of hepatotoxicity, nephrotoxicity, nausea, altered taste, anemia, GI upsets, hair loss, and so forth. due to conventional oral treatment approaches. Conclusion: Adoption of the remedial approach can be recommended after preclinical trials' approval as a safe treatment.

Impact of Active Antihyperglycemic Components as Herbal Therapy for Preventive Health Care Management of Diabetes.

Diabetes is a metabolic hyperglycemic condition that progressively develops, effect small and large sensory fibers in the affected population. It has various complications as hypertension, coronary artery disease, stroke, blindness, kidney disease as well as peripheral neuropathy. Sulfonylureas, thiazolidinediones, metformin, biguanidine, acarbose and insulin are commonly used drugs for diabetic patients, but these all have certain side effects. Even metformin, that is known as the miracle drug for diabetes has been found to be associated with side effects, as during treatment it involves complications with eyes, kidneys, peripheral nerves, heart and vasculature. In the present article, we hypothesize recent discoveries with respect to active ingredients from Indian medicinal plants i.e., polypeptide-p (protein analogue act as artificial insulin), charantin (a steroidal saponin), momordicin (an alkaloid) and osmotin (ubiquitous plant protein and animal analogue of human adeponectin) possessing anti-hyperglycemic potential for diabetes type II. Therefore, plants as herbal therapy have preventive care of hyperglycemia accompanied with healthy lifestyle which can provide significant decline in the incidences of diabetes in future.

The protective effect of α-lipoic acid against bisphenol A-induced neurobehavioral toxicity.

Bisphenol A (BPA), a well-known xenoestrogen, is ubiquitously utilized in manufacturing of polycarbonated plastics. Convincing evidence suggests that BPA induces neurotoxicity and certain behavioral deficits. α-Lipoic acid (ALA) supplementation has shown protective effect against heart and liver diseases, diabetes, and neurological debility associated with aging. We studied the neuromodulatory effect of ALA against neurotoxicity of BPA in vitro in C8-D1A mouse astrocyte cell line and in vivo in C57BL/6J male mice. In vitro ALA (100 µM) protected cells from BPA (30 µM)-induced reactive oxygen species generation and increased activity of glial fibrillary acidic protein. ALA showed reduction in cell death in astrocytes treated with BPA. In vivo ALA (50 mg/kg) increased the neurospecific acetylcholinesterase activity and decreased the monoamine oxidase activity altered by BPA exposure (10 mg/kg, per os x 30 days). In addition to neuroprotective effects, ALA also showed protective effects against BPA-induced oxidative stress. We observed that ALA significantly replenished the declined neurobehavioral and cognitive performances, decreased muscle coordination and alerted short-term recognition memory in mice exposed to BPA. Our results suggest that ALA has a promising role in modulating BPA-induced neurotoxicity in C8-D1A mouse astrocyte cells as well as neurochemical and neurobehavioral deficits in C57BL/6J male mice and its antioxidant and free radical scavenging activities may in part be responsible for such an effect.

Homocysteine alters the osteoprotegerin/RANKL system in the osteoblast to promote bone loss: pivotal role of the redox regulator forkhead O1.

In this study we determined the molecular mechanisms of how homocysteine differentially affects receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) synthesis in the bone. The results showed that oxidative stress induced by homocysteine deranges insulin-sensitive FOXO1 and MAP kinase signaling cascades to decrease OPG and increase RANKL synthesis in osteoblast cultures. We observed that downregulation of insulin/FOXO1 and p38 MAP kinase signaling mechanisms due to phosphorylation of protein phosphatase 2A (PP2A) was the key event that inhibited OPG synthesis in homocysteine-treated osteoblast cultures. siRNA knockdown experiments confirmed that FOXO1 is integral to OPG and p38 synthesis. Conversely homocysteine increased RANKL synthesis in osteoblasts through c-Jun/JNK MAP kinase signaling mechanisms independent of FOXO1. In the rat bone milieu, high-methionine diet-induced hyperhomocysteinemia lowered FOXO1 and OPG expression and increased synthesis of proresorptive and inflammatory cytokines such as RANKL, M-CSF, IL-1α, IL-1ß, G-CSF, GM-CSF, MIP-1α, IFN-γ, IL-17, and TNF-α. Such pathophysiological conditions were exacerbated by ovariectomy. Lowering the serum homocysteine level by a simultaneous supplementation with N-acetylcysteine improved OPG and FOXO1 expression and partially antagonized RANKL and proresorptive cytokine synthesis in the bone milieu. These results emphasize that hyperhomocysteinemia alters the redox regulatory mechanism in the osteoblast by activating PP2A and deranging FOXO1 and MAPK signaling cascades, eventually shifting the OPG:RANKL ratio toward increased osteoclast activity and decreased bone quality.

Effect of vitamin D supplementation during pregnancy on neonatal mineral homeostasis and anthropometry of the newborn and infant.

Hypovitaminosis D is common in India. In the present prospective partially randomised study of vitamin D (D3) supplementation during pregnancy, subjects were randomised in the second trimester to receive either one oral dose of 1500 µg vitamin D3 (group 1, n 48) or two doses of 3000 µg vitamin D3 each in the second and third trimesters (group 2, n 49). Maternal 25-hydroxyvitamin D (25(OH)D) at term, cord blood (CB) alkaline phosphatase (ALP), neonatal serum Ca and anthropometry were measured in these subjects and in forty-three non-supplemented mother-infant pairs (usual care). Median maternal 25(OH)D at term was higher in group 2 (58·7, interquartile range (IQR) 38·4-89·4 nmol/l) v. group 1 (26·2, IQR 17·7-57·7 nmol/l) and usual-care group (39·2, IQR 21·2-73·4 nmol/l) (P = 0·000). CB ALP was increased (>8.02 µkat/l or >480 IU/l) in 66·7 % of the usual-care group v. 41·9 % of group 1 and 38·9 % of group 2 (P = 0·03). Neonatal Ca and CB 25(OH)D did not differ significantly in the three groups. Birth weight, length and head circumference were greater and the anterior fontanelle was smaller in groups 1 and 2 (3·08 and 3·03 kg, 50·3 and 50·1 cm, 34·5 and 34·4 cm, 2·6 and 2·5 cm, respectively) v. usual care (2·77 kg, 49·4, 33·6, 3·3 cm; P = 0·000 for length, head circumference and fontanelle and P = 0·003 for weight). These differences were still evident at 9 months. We conclude that both 1500 µg and two doses of 3000 µg vitamin D3 had a beneficial effect on infant anthropometry, the larger dose also improving CB ALP and maternal 25(OH)D.

Construction of genetic linkage map of the medicinal and ornamental plant Catharanthus roseus.

An integrated genetic linkage map of the medicinal and ornamental plant Catharanthus roseus, based on different types of molecular and morphological markers was constructed, using a F(2) population of 144 plants. The map defines 14 linkage groups (LGs) and consists of 131 marker loci, including 125 molecular DNA markers (76 RAPD, 3 RAPD combinations; 7 ISSR; 2 EST-SSR from Medicago truncatula and 37 other PCR based DNA markers), selected from a total of 472 primers or primer pairs, and six morphological markers (stem pigmentation, leaf lamina pigmentation and shape, leaf petiole and pod size, and petal colour). The total map length is 1131.9 cM (centiMorgans), giving an average map length and distance between two markers equal to 80.9 cM and 8.6 cM, respectively. The morphological markers/genes were found linked with nearest molecular or morphological markers at distances varying from 0.7 to 11.4 cM. Linkage was observed between the morphological markers concerned with lamina shape and petiole size of leaf on LG1 and leaf, stem and petiole pigmentation and pod size on LG8. This is the first genetic linkage map of C. roseus.