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. Objectives: Analysis of plasma metabolites and related pathways to classify Prakriti specific dominant marker metabolites and metabolic pathways. Materials and methods: 38 healthy male individuals were assessed for dominant Prakritis and their fasting blood samples were collected. The processed plasma samples were subjected to rapid resolution liquid chromatography–electrospray ionization–quadrupole time of flight mass spectrometry (RRLC–ESI–QTOFMS). Mass profiles were aligned and subjected to multivariate analysis. Results: Partial least square discriminant analysis (PLS-DA) model showed 97.87% recognition capability. List of PLS-DA metabolites was subjected to permutative Benjamini–Hochberg false discovery rate (FDR) correction and final list of 76 metabolites with p  2.0 was identified. Pathway analysis using metascape and JEPETTO plugins in Cytoscape revealed that steroidal hormone biosynthesis, amino acid, and arachidonic acid metabolism are major pathways varying with different constitution. Biological Go processes analysis showed that aromatic amino acids, sphingolipids, and pyrimidine nucleotides metabolic processes were dominant in kapha type of body constitution. Fat soluble vitamins, cellular amino acid, and androgen biosynthesis process along with branched chain amino acid and glycerolipid catabolic processes were dominant in pitta type individuals. Vata Prakriti was found to have dominant catecholamine, arachidonic acid and hydrogen peroxide metabolomics processes. Conclusion: The neurotransmission and oxidative stress in vata, BCAA catabolic, androgen, xenobiotics metabolic processes in pitta, and aromatic amino acids, sphingolipid, and pyrimidine metabolic process in kapha Prakriti were the dominant marker pathways. Keywords: Ayurveda, Prakriti, Human metabolomics, RRLC–ESI–QTOFM

β-sitosterol in different parts of Saraca asoca and herbal drug ashokarista: Quali-quantitative analysis by liquid chromatography-mass spectrometry

β-sitosterol is an important component in food and herbal products and beneficial in hyperlipidemia. Its higher concentrations in serum may lead to coronary artery disease in case of sitosterolemia. Therefore, it is essential to determine the quantity of β-sitosterol in food and herbal drugs. Saraca asoca and its preparations have been widely used by traditional healers are also a source of β-sitosterol. In the present study, quantitative estimation of β-sitosterol present in hot and cold water extracts of bark, regenerated bark, leaves and flowers of the S. asoca and Ashokarista drugs were carried out first time using high performance liquid chromatography coupled (HPLC) with quadrupole time-of-flight mass spectrometry. Different concentrations of β-sitosterol and crude extracts were estimated by HPLC and targeted mass spectrometry. Standard curve for β-sitosterol was prepared from the intensities of transitions (397.50 → 147.0987 m/z) having regression coefficient (r 2) 0.9952. Out of eight extracts and two drugs used in the study bark water, leaves water and leaves hot water extracts were found to have a considerable quantity of β-sitosterol, i.e. 170, 123.5 and 19.3 ng/mL, respectively. The results showed significant differences in the distribution of β-sitosterol among different organs of S. asoca and drugs prepared from its bark. HPLC/electrospray ionizationmass spectroscopy method is accurate, reproducible and requires less specimen, sample preparation and analysis time over HPLC assay. This type of approaches could be helpful for the quality control of herbal medicines and provides necessary information for the rational utilization of plant resources

Quantitative analysis of catechins in Saraca asoca and correlation with antimicrobial activity

Herbal medicines are highly complex and have unknown mechanisms in diseases treatment. Saraca asoca (Roxb.), De. Wild has been recommended to treat gynecological disorders and used in several commercial polyherbal formulations. In present study, efforts have been made to explore antimicrobial activity and its co-relation with the distributions of catechins in the organs of S. asoca using targeted MS/MS. Eight extracts (cold and hot water) from four different organs of S. asoca and two drugs were prepared and antimicrobial activity was assessed by microbroth dilution assay. Quantitative and qualitative analysis of catechins in crude extracts was done by using targeted and auto-MS/MS and correlated with antimicrobial activity. (+)-Catechin and (+)-epicatechin and their biosynthesis related compound were found to be up-regulated in regenerated bark and leaves extracts. (â)-Epigallocatechin was found to be significantly higher in bark water extract as compared to others but showed low antimicrobial activity. Result showed down-regulation of (â)-epigallocatechin and up-regulation of (+)-catechin and (+)-epicatechin in the regenerated bark and leaves of S. asoca. It might be the contributing factor in the antimicrobial activity of regenerated bark and leaves of the plant. The concentration of (+)-epicatechin in processed drugs (Ashokarishta) from Baidyanath was found to be seven times higher than that of Dabur Pvt. Ltd., but no antimicrobial activity was observed, indicating the variations among the plant based drugs. This will be helpful in rational use of S. asoca parts. Furthermore, the analytical method developed is sensitive, repeatable and reliable; therefore, it is suitable for quality control of herbal drugs. Keywords: Mass spectroscopy, Phytochemistry, Quality control, Flavonoids, Ayurveda, Antimicrobia

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-1H-pyrrole-2-carboxamides 3a–m and carbohydrazide analogues 5a–l 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. The compounds 5h, 5i and 5j were found to be the most potent against Aspergillus fumigatus, with MIC values of 0.039 mg/mL. The compound 5f bearing a 2, 6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with a MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking with the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron-related deleterious side effects observed with many existing antifungal compounds

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. This paper reviews the mechanisms of action of all these drugs by broadly classifying them into six different categories. Mechanistic data of these drugs illustrate that they regulate skeletal muscle loss either by down-regulating myostatin, cyclooxygenase2, pro-inflammatory cytokines mediated catabolic wasting or by up-regulating cyclic AMP, peroxisome proliferator-activated receptor gamma coactivator-1α, growth hormone/insulin-like growth factor1, phosphatidylinositide 3-kinases/protein kinase B(Akt) mediated anabolic pathways. So far, five major proteolytic systems that regulate loss of muscle mass have been identified, but the majority of these drugs control only two or three proteolytic systems. In addition to their beneficial effect on restoring the muscle loss, many of these drugs show some level of toxicity and unwanted side effects such as dizziness, hypertension, and constipation. Therefore, further research is needed to understand and develop treatment strategies for muscle wasting. For successful management of skeletal muscle wasting either therapeutic agent which regulates all five known proteolytic systems or new molecular targets/proteolytic systems must be identified

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. Bearing this goal in mind, the article reviews the mechanisms of action of available anti-diabetic drugs with in-depth mechanistic analysis of each therapy. The conventional and herbal strategies are analysed and compared for their benefits and the associated possible side effects. This critical information is necessary not only for the development of better, novel and potent anti-diabetic therapy in future but also for best possible combinational therapies and strategies with the available drugs

Antimicrobial Activity of Some Indian Medicinal Plants

The antimicrobial potential of seventy-seven extracts from twenty-four plants was screened against eight bacteria and four pathogenic fungi, using microbroth dilution assay. Lowest concentration of the extract, which inhibits any visual microbial growth after treatment with p-iodonitrotetrazolium violet, was considered to be minimum inhibitory concentration (MIC). Water extracts of Acacia nilotica, Justicia zelanica, Lantana camara and Saraca asoca exhibited good activity against all the bacteria tested and the MIC was recorded in range of 9.375–37.5 µg/ml and 75.0–300.0 µg/ml against the bacterial and fungal pathogens, respectively. The other extracts of Phyllanthus urinaria, Thevetia nerifolia, Jatropha gossypifolia Saraca asoca, Tamarindus indica, Aegle marmelos, Acacia nilotica, Chlorophytum borivilianum, Mangifera indica, Woodfordia fruticosa and Phyllanthus emblica showed antimicrobial activity in a range of 75–1200 µg/ml

<i>In Vivo</i> Efficacy of a Synthetic Coumarin Derivative in a Murine Model of Aspergillosis

<div><p>Despite advances in therapeutic modalities, aspergillosis remains a leading cause of mortality. This has necessitated the identification of effective and safe antifungal molecules. In the present study, <i>in vivo</i> safety and antifungal efficacy of a coumarin derivative, <i>N</i>, <i>N, N</i>-Triethyl-11-(4-methyl-2-oxo-2<i>H</i>-benzopyran-7-yloxy)-11-oxoundecan-1-aminium bromide (SCD-1), was investigated. The maximum tolerable dose of compound was determined according to OECD 423 guidelines. The compound could be assigned to category IV of the Globally Harmonized System and its LD₅₀ cut-off was found to be 2000 mg/kg body weight. The survival increased in <i>Aspergillus fumigatus-</i>infected mice treated with a dose of 200 mg/kg, orally or 100 mg/kg body weight, intraperitoneally, of SCD-1 in comparison to infected-untreated animals. The SCD-1 treatment resulted in significant reduction in colony counts in vital organs of the animals. Its protective effect was also observed on day 14 as there was marked reduction in fungal colonies. The treatment with SCD-1 also reduced the levels of serum biochemical parameters with respect to infected-untreated animals. It could be concluded that SCD-1 is a quite safe antifungal compound, which conferred dose dependent protection against experimental aspergillosis. Therefore, SCD-1 holds potential for developing new formulations for aspergillosis.</p></div

Body weights of experimental mice.

<p>The daily weight (Mean ± SE) of animals belonging to different groups was recorded daily over a period of 14 days.</p