Recent Advances in Targeting Transition Metals (Copper, Iron, and Zinc) in Alzheimer's Disease.

Changes in the transition metal homeostasis in the brain are closely linked with Alzheimer's disease (AD), including intraneuronal iron accumulation and extracellular copper and zinc pooling in the amyloid plague. The brain copper, zinc, and iron surplus are commonly acknowledged characteristics of AD, despite disagreements among some. This has led to the theory that oxidative stress resulting from abnormal homeostasis of these transition metals may be a causative explanation behind AD. In the nervous system, the interaction of metals with proteins appears to be an essential variable in the development or suppression of neurodegeneration. Chelation treatment may be an option for treating neurodegeneration induced by transition metal ion dyshomeostasis. Some clinicians even recommend using chelating agents as an adjunct therapy for AD. The current review also looks at the therapeutic strategies that have been attempted, primarily with metal-chelating drugs. Metal buildup in the nervous system, as reported in the AD, could be the result of compensatory mechanisms designed to improve metal availability for physiological functions.

Ashwagandha: Advances in plant biotechnological approaches for propagation and production of bioactive compounds.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera is one of the most extensively delved Ayurvedic medicine. Apart from rejuvenation and increasing longevity, it has several other properties such as immunomodulation, anti-cancer, anti-stress and neuroprotection. Because of its prevailing use and increasing demand, it becomes prudent to scientifically evaluate and document both its propagation and production of desired phytoconstituents. AIM OF THE STUDY: This review aims to highlight the research progress achieved on various biotechnological and tissue culture aspects of Withania somnifera and to cover up-to-date information regarding in-vitro propagation and production of withanolides. MATERIALS AND METHODS: Significant published studies were identified for the years 2000-2018 using Elsevier-Science Direct, Pubmed and Google scholar and several research studies in our laboratory. Following keywords such as "plant extracts", "in vitro cultures", "callus and suspension culture", "micropropagation", "hairy root cultures" were used. Further, "Withania somnifera", "secondary metabolites specially withanolides", "molecular techniques" and "in vitro conservation" were used to cross-reference the keywords. RESULTS: Ashwagandha comprises a broad spectrum of phytochemicals with a wide range of pharmacological properties. W. somnifera seeds have reduced viability and germination rates; thus, its regular cultivation method fails to achieve commercial demands mainly for the production of desired phytoconstituents. Cultivation of plant cells/tissues under in vitro conditions and development of various biotechnological strategies will help to build an attractive alternative to provide adequate quality and quantity raw materials. Recently, a large number of in vitro protocols has developed for W. somnifera not only for its propagation but for the production of secondary metabolites as well. Present work highlights a variety of biotechnological strategies both for prompt propagation and production of different bioactive secondary metabolites. CONCLUSION: The present review focuses on the development and opportunities in various biotechnological approaches to accomplish the global demand of W. somnifera and its secondary metabolites. This review underlines the advances in plant biotechnological approaches for the propagation of W. somnifera and production of its bioactive compounds.

Pharmacological evaluation of Ashwagandha highlighting its healthcare claims, safety, and toxicity aspects.

Withania somnifera, commonly known as "Ashwagandha" or "Indian ginseng" is an essential therapeutic plant of Indian subcontinent regions. It is regularly used, alone or in combination with other plants for the treatment of various illnesses in Indian Systems of Medicine over the period of 3,000 years. Ashwagandha (W. somnifera) belongs to the genus Withania and family Solanaceae. It comprises a broad spectrum of phytochemicals having wide range of biological effects. W. somnifera has demonstrated various biological actions such as anti-cancer, anti-inflammatory, anti-diabetic, anti-microbial, anti-arthritic, anti-stress/adaptogenic, neuro-protective, cardio-protective, hepato-protective, immunomodulatory properties. Furthermore, W. somnifera has revealed the capability to decrease reactive oxygen species and inflammation, modulation of mitochondrial function, apoptosis regulation and improve endothelial function. Withaferin-A is an important phytoconstituents of W. somnifera belonging to the category of withanolides been used in the traditional system of medicine for the treatment of various disorders. In this review, we have summarized the active phytoconstituents, pharmacologic activities (preclinical and clinical), mechanisms of action, potential beneficial applications, marketed formulations and safety and toxicity profile of W. somnifera.

Flavonoids as Multi-Target Compounds: A Special Emphasis on their Potential as Chemo-adjuvants in Cancer Therapy.

Flavonoids are low molecular weight, polyphenolic phytochemicals, obtained from secondary metabolism of various plant compounds. They have a spectrum of pharmacological efficacies, including potential anticancer efficacy. Natural flavonoids are present in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. Flavonoids can attenuate or inhibit the initiation, promotion and progression of cancer by modulating various enzymes and receptors in diverse pathways that involve cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis and metastasis. Furthermore, in vitro, flavonoids have been shown to reverse multidrug resistance when used as chemo-adjuvants. Flavonoids (both natural and synthetic analogues) interact with several oncogenic targets through dependent and independent mechanisms to mediate their anticancer efficacy in different types of cancer cells.

Metabolic characterization of Withania somnifera from different regions of India using NMR spectroscopy.

Withania somnifera (L.) Dun. (Solanaceae), known as Indian ginseng, is one of the most popular medicinal plants in India. Considering the importance and common use of this plant, it is necessary to investigate its holistic metabolite profile. However, with existing analytical methods which are based on TLC and HPLC­UV (or MS), it is difficult to obtain information of the whole range of compounds appropriately. In this study, the metabolic characterization of Withania somnifera leaves, stems, and roots collected in six different regions in India was performed using ¹H NMR spectroscopy followed by principal component analysis (PCA) and hierarchical clustering analysis (HCA). Of the parts of Withania somnifera analyzed in this study, the leaf was found to have the widest range of metabolites, including amino acids, flavonoids, lipids, organic acids, phenylpropanoids, and sugars, as well as the main secondary metabolites of the plant, withanolides. The ¹H NMR spectra revealed the presence of two groups of withanolides: 4-OH and 5,6-epoxy withanolides (withaferin A-like steroids) and 5- OH and 6,7-epoxy withanolides (withanolides Alike steroids). The ratio of these two withanolides was found to be a key discriminating feature of Withania somnifera leaf samples from different origins.

Broad-spectrum sun-protective action of Porphyra-334 derived from Porphyra vietnamensis.

There are enormous UV-protective compounds present in the current world market, out of which 98% give protection against UV-B range and the remaining 2% are potent against far UV-A range only. Furthermore, these synthetic compounds have various problems related to photo-stability and cross-stability. There is a vital need of sunscreen agents that will remain stable for prolonged periods and provide broad-spectrum protection against harmful UV range. The Indian Ocean contains large amounts of macro-algae which synthesize varied amount of mycosporine amino acids, "sun-protective compounds" by shikmic acid pathway. In the present study, we have evaluated the sunscreen protection provided by Porphyra-334, a mycosporine amino acid isolated from Indian sp. of Porphyra. Furthermore, the isolated compound was detected by high performance thin layer chromatography (HPTLC) fingerprinting, high performance liquid chromatography (HPLC) and ultraviolet (UV), whereas nuclear magnetic resonance (NMR) spectroscopy and infrared spectrometry were used for its structural characterization. Stability studies were performed under different storage and pH conditions. Ultimately a sunscreen formulation was developed and its potential against marketed Aloe vera gel was evaluated by in vitro sunscreen protection method. It was observed that sunscreen potential of Porphyra-334 was 5.11-fold greater than that of the marketed Aloe vera gel preparation.

Development and validation of a TLC-densitometric method for the simultaneous quantitation of strychnine and brucine from Strychnos spp. and its formulations.

A simple, sensitive, and specific thin-layer chromatography densitometric method has been developed for the simultaneous quantitation of strychnine and brucine. These two marker compounds are quantitated in the seeds of Strychnos nux-vomica, Strychnos ignatii, and its formulations. The method involves densitometric evaluation of strychnine and brucine after resolving it by high-performance TLC on silica gel plate with toluene-ethyl acetate-diethyl amine-methanol (7:2:1:0.3 v/v) as the mobile phase. The method is validated for precision (interday and intraday), repeatability, and accuracy. The relationship between the concentration of standard solutions and the peak response is linear within the concentration range of 160 to 480 ng/spot for strychnine and 80 to 480 ng/spot for brucine. Instrumental precision is found to be 0.54 and 0.78 (% CV), and repeatability of the method is 1.01 and 1.06 (% CV) for strychnine and brucine, respectively. Accuracy of the method is checked by recovery study conducted at three different levels and the average percentage recovery is found to be 99.13% for strychnine and 100.16% for brucine. The proposed HPTLC method for the simultaneous quantitation of strychnine and brucine is found to be simple, precise, specific, sensitive, and accurate, and it can be used for routine quality control of raw material of Strychnos spp. It also can be applied in quantitating any of these marker compounds in other formulations.

Rapid densitometric method for simultaneous analysis of umbelliferone, psoralen, and eugenol in herbal raw materials using HPTLC.

The term 'phenolics' refers to a vast array of biologically active compounds ubiquitous in plants, many of which have been used in traditional medicine for thousands of years. Umbelliferone, psoralen, and eugenol are widely occurring phenolic compounds of plant origin, for which many biological activities against chronic diseases have been reported. A simple HPTLC method has been developed for the simultaneous quantification of umbelliferone, psoralen, and eugenol. These three compounds were quantified in the dried fruit pulp of Aegle marmelos and in the fruit of Trachyspermum ammi and Foeniculam vulgare. The technique enables rapid and sensitive simultaneous analysis in different samples. The method was validated for precision, repeatability, and accuracy in accordance with ICH guidelines. The accuracy of the method was checked by a recovery study conducted at three different levels and the average percentage recovery was found to be 98.88% for umbelliferone, 100.104% for psoralen, and 99.33% for eugenol. The proposed HPTLC method for the simultaneous quantification of umbelliferone, psoralen, and eugenol was found to be simple, precise, specific, sensitive, and accurate. It can be used for routine quality control of herbal raw materials as well as formulations containing any or all of these compounds.