A Systematic Review on Traumatic Brain Injury Pathophysiology and Role of Herbal Medicines in its Management.

BACKGROUND: Traumatic brain injury (TBI) is a worldwide problem. Almost about sixtynine million people sustain TBI each year all over the world. Repetitive TBI linked with increased risk of neurodegenerative disorder such as Parkinson, Alzheimer, traumatic encephalopathy. TBI is characterized by primary and secondary injury and exerts a severe impact on cognitive, behavioral, psychological and other health problem. There were various proposed mechanism to understand complex pathophysiology of TBI but still there is a need to explore more about TBI pathophysiology. There are drugs present for the treatment of TBI in the market but there is still need of more drugs to develop for better and effective treatment of TBI, because no single drug is available which reduces the further progression of this injury. OBJECTIVE: The main aim and objective of structuring this manuscript is to design, develop and gather detailed data regarding about the pathophysiology of TBI and role of medicinal plants in its treatment. METHOD: This study is a systematic review conducted between January 1995 to June 2021 in which a consultation of scientific articles from indexed periodicals was carried out in Science Direct, United States National Library of Medicine (Pubmed), Google Scholar, Elsvier, Springer and Bentham. RESULTS: A total of 54 studies were analyzed, on the basis of literature survey in the research area of TBI. CONCLUSION: Recent studies have shown the potential of medicinal plants and their chemical constituents against TBI therefore, this review targets the detailed information about the pathophysiology of TBI and role of medicinal plants in its treatment.

Homeopathic Medicines in Second Wave of COVID-19: Prognostic Factor Research.

BACKGROUND: The clinical profile and course of COVID-19 evolved perilously in a second wave, leading to the use of various treatment modalities that included homeopathy. This prognostic factor research (PFR) study aimed to identify clinically useful homeopathic medicines in this second wave. METHODS: This was a retrospective, multi-centred observational study performed from March 2021 to May 2021 on confirmed COVID-19 cases who were either in home isolation or at COVID Care Centres in Delhi, India. The data were collected from integrated COVID Care Centres where homeopathic medicines were prescribed along with conventional treatment. Only those cases that met a set of selection criteria were considered for analysis. The likelihood ratio (LR) was calculated for the frequently occurring symptoms of the prescribed medicines. An LR of 1.3 or greater was considered meaningful. RESULTS: Out of 769 confirmed COVID-19 cases reported, 514 cases were selected for analysis, including 467 in home isolation. The most common complaints were cough, fever, myalgia, sore throat, loss of taste and/or smell, and anxiety. Most cases improved and there was no adverse reaction. Certain new symptoms, e.g., headache, dryness of mouth and conjunctivitis, were also seen. Thirty-nine medicines were prescribed, the most frequent being Bryonia alba followed by Arsenicum album, Pulsatilla nigricans, Belladonna, Gelsemium sempervirens, Hepar sulphuris, Phosphorus, Rhus toxicodendron and Mercurius solubilis. By calculating LR, the prescribing indications of these nine medicines were ascertained. CONCLUSION: Add-on use of homeopathic medicines has shown encouraging results in the second wave of COVID-19 in integrated care facilities. Further COVID-related research is required to be undertaken on the most commonly prescribed medicines.

Effects of the COVID-19 pandemic on semen quality in male partners of infertile couples: a hospital-based observational study.

The effects of the coronavirus disease 2019 (COVID-19) pandemic on male fertility have received considerable attention because human testes contain high levels of angiotensin-converting enzyme-2 receptors, through which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enter. Early studies showed decreases in semen quality during and after recovery from COVID-19. However, no semen quality studies have examined the effects of widespread subclinical and mild disease, as well as changes in lifestyle, psychosocial behavior, intake of dietary supplements, and stress. This cross-sectional study compared semen quality parameters in male partners of infertile couples between men who underwent semen analysis before the COVID-19 pandemic (prepandemic group) and men who underwent semen analysis during the pandemic period (pandemic group); the analysis sought to clarify the overall effects of the pandemic. No participants in the pandemic group had experienced clinically overt disease. Among the 239 participants, mean body weight (P = 0.001), mean body mass index (P < 0.001), median sperm concentration (P = 0.014), total sperm count (P = 0.006), and total percentages of motile (P = 0.013) and abnormal cells (P < 0.001) were significantly greater in the pandemic group (n = 137) than those in the prepandemic group (n = 102). Among abnormal cells, the percentages of cells with excess residual cytoplasm (P < 0.001), head defects (P < 0.001), and tail defects (P = 0.015) were significantly greater in the pandemic group than those in the prepandemic group. With the exception of morphology, the overall semenogram results were better in the pandemic group than those in the prepandemic group.

The Effectiveness of Rajyoga Meditation as an Adjuvant for Panic Anxiety Syndrome.

Objective: One of the most prevalent psychiatric conditions that affect a person's quality of life, ability to function and productivity, and consequently the loss of national income, are anxiety disorders. Rajyoga meditation (RM) is a form of meditation that is performed without rituals or mantras and can be practiced anywhere at any time. In this study, we attempted to evaluate the modulation of psycho-physiological parameters in panic disorder patients by a technique of short-term on RM. Methods: In this prospective randomized control study, 110 patients with panic disorder were randomized into two groups, Group A (standard treatment + RM) and Group B (Standard treatment). The participants of both group participants were subjected to sleep quality score, Physical Health Questionnaire-9 score, Panic Disorder Severity Scale (PDSS), and Hamilton Anxiety Rating Scale (HAM-A) questionnaires before starting the study (baseline) and at the end of the 8th week. Study groups were compared at baseline and at the end of 8 weeks. Results: We found that the PDSS/HAM-A was not statistically different among the study groups at baseline (P > 0.05); however, there was a statistically significant difference in mean z-scores of PDSS and post-HAM-A scores among the study groups at 8 weeks (P < 0.001). The composite score was created by adding the z-scores of pre- and post-PDSS and HAM-A. We found a statistically significant difference in postcomposite scores between the study groups (P < 0.001). Analysis of co-variance for PDSS and HAM-A among study groups showed statistical significance (P < 0.001). Conclusion: When used in conjunction with pharmaceutical treatments for the treatment of panic disorder, RM is a successful therapy. The key factors are adherence and motivation while being supervised by a licensed therapist.

Computational investigation of natural compounds as potential main protease (Mpro) inhibitors for SARS-CoV-2 virus.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is significantly impacting human lives, overburdening the healthcare system and weakening global economies. Plant-derived natural compounds are being largely tested for their efficacy against COVID-19 targets to combat SARS-CoV-2 infection. The SARS-CoV-2 Main protease (Mpro) is considered an appealing target because of its role in replication in host cells. We curated a set of 7809 natural compounds by combining the collections of five databases viz Dr Duke's Phytochemical and Ethnobotanical database, IMPPAT, PhytoHub, AromaDb and Zinc. We applied a rigorous computational approach to identify lead molecules from our curated compound set using docking, dynamic simulations, the free energy of binding and DFT calculations. Theaflavin and ginkgetin have emerged as better molecules with a similar inhibition profile in both SARS-CoV-2 and Omicron variants.

Onion waste based-biorefinery for sustainable generation of value-added products.

Waste derived from the onion processing sector can be harnessed for the production of organic acids, polyphenols, polysachharides, biofuels and pigments. To sustainably utilize onion processing residues, different biorefinery strategies such as enzymatic hydrolysis, fermentation and hydrothermal carbonization have been widely investigated. This review discusses the recent advances in the biorefinery approaches used for valorization of onion processing waste followed by the production of different value-added products from diverse classes of onion waste. The review also highlights the current challenges faced by the bioprocessing sector for the utilization of onion processing waste and perspectives to tackle them.

Advances in bioconversion of spent tea leaves to value-added products.

Spent tea leaves (STL) are generated after the extraction of liquor from processed tea leaves and are regarded as an underutilized waste. STL are rich in essential amino acids, ω-6 and ω-3 fatty acids, alkaloids (theobromine and caffeine), polyphenols (catechin, theaflavins and rutin) and minerals (Ca, P, K, Mg, Mn) that could be utilized for the production of industrially important products. Vermicomposting, anaerobic digestion, silage preparation and fermentation are currently used as low cost methods for the bioconversion of STL to a usable form. Structural, morphological and chemical modification of STL after suitable bioconversion enables its application in the development of biopolymers, biofuels, catechin derivatives, biochar, absorbents for dye, and for removal of Cd, Hg, Cr(IV), As(V) and aspirin. This review discusses the composition, characterization, bioconversion and value added product generation from STL while highlighting prospective applications of STL in developing battery electrodes, nanocatalysts, insulation materials and edible bioactive peptides.

Effect of microwave treatment (low power and varying time) on potato starch: Microstructure, thermo-functional, pasting and rheological properties.

The present study focused on the effect of microwave treatment (300 W for 1, 3 and 5 min) on the physicochemical, morphological, structural and rheological properties of potato starch. Significant effect (p < 0.05) of treatment time was observed on water activity and moisture content while non-significant effect occurred on color. Water absorption capacity increased from 0.82-1.16 g/g with treatment time while oil absorption capacity decreased from 0.63-0.53 g/g. Dynamic and loss moduli, pasting temperatures and final viscosities were positively correlated with treatment time. The peak and pasting viscosity incremented till 3 min treatment but decreased at 5 min. Onset temperature of gelatinization ranged from 53.8 to 57.4 °C with treatment time. SEM micrographs showed unaffected starch granules at 1 min of treatment while fissures and indentations developed at 3 and 5 min. The X-Ray diffraction patterns indicated the transformation of starch crystals from B crystallite to amorphic type.

Brevifoliol ester induces apoptosis in prostate cancer cells by activation of caspase pathway.

Prostate cancer is fourth most abundant cancer type around the globe. Brevifoliol, a rearranged taxoid from Taxus walllichiana needles has been derivatized as C5 esters using Steglich esterification reaction. Seventeen diverse analogues were evaluated against a panel of human cancer cell lines by MTT assay. Among these, two of the semi-synthetic analogues, that is, 13 and 16 exhibited potent cytotoxicity, selectively against PC-3, prostate cancer cell lines. In cell cycle analysis, analogue 13 induced S and G2/M phase arrest and induced apoptosis by activating caspase-3. Compound 13 showed moderate efficacy in in-vivo Ehrlich ascites carcinoma in Swiss albino mice. Further, compound 13 was found to be safe in Swiss albino mice up to 1,000 mg/kg dose in acute oral toxicity. Brevifoliol ester 13 may further be optimized for better efficacy.

Bixin Triggers Apoptosis of Human Hep3B Hepatocellular Carcinoma Cells: An Insight to Molecular and IN SILICO Approach.

Hepatocellular carcinoma (HCC) is the most common liver cancer and is known to be resistant to conventional chemotherapy. The use of herbal medicine and supplements has increased over recent decades following side effects and resistant to conventional chemotherapy. The seeds of Bixa orellana L. commonly known as annatto have recently gained scientific attention due to presence of a carotenoid bixin for its substantial anticancer properties. However, molecular mechanisms underlying bixin-induced apoptosis are still unclear. Treatment of bixin significantly decreased the number of Hep3B cells and morphological study revealed the change in cellular and nuclear morphology that trigger the events of apoptosis confirmed by annexin V/PI staining. Further DCFDA and rhodamine 123 spectrofluorimetry study showed elevation in reactive oxygen species (ROS) production and loss of mitochondrial membrane potential (MMP), respectively. ROS production caused DNA damage and apoptosis was marked by cell cycle arrest, up-regulation of Bax and FasL protein as well as cleavage of caspase-9, caspase-8 and caspase-3 protein. Docking study with pro-apoptotic molecule Bax and surface Fas ligand exhibited energetically favourable binding interaction. Collectively, these results suggest that bixin capable of modulating the extrinsic and intrinsic molecules of apoptosis indicating its potential for development of promising candidate for hepatocellular carcinoma.

AromaDb: A Database of Medicinal and Aromatic Plant's Aroma Molecules With Phytochemistry and Therapeutic Potentials.

In traditional, herbal medicine, and aromatherapy, use of essential oils and their aroma compounds have been known since long, for the management of various human diseases. The essential oil is a mixture of highly complex, naturally occurring volatile aroma compounds synthesized by medicinal and aromatic plants as secondary metabolites. Essential oils widely used in pharmaceutical, cosmetic, sanitary, food industry and agriculture for their antibacterial, antiviral, antifungal, antiparasitic, insecticidal, anticancer, neuroprotective, psychophysiological, and anti-aging activities. Moreover, volatile aroma compounds comprise a chemically diverse class of low molecular weight organic compounds with significant vapor pressure. However, aroma compounds produced by plants, mainly attract pollinators, seed dispersers and provide defense against pests or pathogens. However, in humans, about 300 active olfactory receptor genes are involved to detect thousands of different aroma compounds and modulates expression of different metabolic genes regulating human psychophysiological activity, brain function, pharmacological signaling, and therapeutic potential. Keeping in mind this importance, present database, namely, AromaDb (http://bioinfo.cimap.res.in/aromadb/) covers information of plant varieties/chemotypes, essential oils, chemical constituents, GC-MS profile, yield variations due to agro-morphological parameters, trade data, aroma compounds, fragrance type, and bioactivity details. The database includes 1,321 aroma chemical structures, bioactivities of essential oil/aroma compounds, 357 fragrance type, 166 commercially used plants, and their high yielding 148 varieties/chemotypes. Also includes calculated cheminformatics properties related to identification, physico-chemical properties, pharmacokinetics, toxicological, and ecological information. Also comprises interacted human genes affecting various diseases related cell signaling pathways correlating the use of aromatherapy. This database could be a useful resource to the plant's growers/producers, an aroma/fragrance industrialist, health professionals, and researchers exploring the potential of essential oils and aroma compounds in the development of novel formulations against human diseases.

Clinical and Neuroimaging Findings in Thalamic Territory Infarctions: A Review.

The thalamus is a part of the diencephalon, containing numerous connections between the forebrain and subcortical structures. It serves an important function as a relay center between the cerebral cortex and the subcortical regions, particularly with sensory information. The thalamus also plays a major role in regulating arousal and the levels of awareness. Distinct vascular distribution of the thalamus give rises to different syndromic presentation of thalamic nuclei infarcts. The clinical records and available imaging studies of patients with confirmed thalamic territory infarcts on magnetic resonance imaging (MRI) at the University Hospital of Rochester were reviewed and analyzed. This analysis was then used to provide an effective summary of thalamic vascular anatomy, the clinical symptoms, and syndromes associated with strokes in the affected territories. Specifically, we review the syndromes associated with classic vascular territories, including the anterior, paramedian, inferolateral, and posterior thalamic nuclei, that are supplied by the polar (tuberothalamic), paramedian, inferolateral (thalamogeniculate), and posterior choroidal arteries, respectively. In addition, we will also review the variant thalamic territories and associated infarction syndromes of the anteromedian, central, and posterolateral territories. This review article is aimed to better the clinical and radiologic understanding as well as the diagnosis of classic and variant thalamic territory infarcts. This article will also briefly touch on the recovery of function after thalamic infarcts.

Chebulinic Acid Isolated From the Fruits of Terminalia chebula Specifically Induces Apoptosis in Acute Myeloid Leukemia Cells.

Chebulinic acid, an ellagitannin found in the fruits of Terminalia chebula, has been extensively used in traditional Indian system of medicine. It has shown to have various biological activities including antitumor activity. The present study aims to investigate the cytotoxic potential of chebulinic acid in human myeloid leukemia cells. Interestingly, chebulinic acid caused apoptosis of acute promyelocytic leukemia HL-60 and NB4 cells but not K562 cells. In vitro antitumor effects of chebulinic acid were investigated by using various acute myeloid leukemia cell lines. Chebulinic acid treatment to HL-60 and NB4 cells induced caspase activation, cleavage of poly(ADP-ribose) polymerase, DNA fragmentation, chromatin condensation, and changes in the mitochondrial membrane permeability. Additionally, inhibition of caspase activation drastically reduced the chebulinic acid-induced apoptosis of acute promyelocytic leukemia cells. Our data also demonstrate that chebulinic acid-induced apoptosis in HL-60 and NB4 cells involves activation of extracellular signal-regulated kinases, which, when inhibited with ERK inhibitor PD98059, mitigates the chebulinic acid-induced apoptosis. Taken together, our findings exhibit the selective potentiation of chebulinic acid-induced apoptosis in acute promyelocytic leukemia cells. Copyright © 2017 John Wiley & Sons, Ltd.

Antimalarial activity and safety assessment of Flueggea virosa leaves and its major constituent with special emphasis on their mode of action.

A clinical emergency stands due to the appearance of drug resistant Plasmodium strains necessitate novel and effective antimalarial chemotypes, where plants seem as the prime option, especially after the discovery of quinine and artemisinin. The present study was aimed towards bioprospecting leaves of Flueggea virosa for its antimalarial efficacy and active principles. Crude hydro-ethanolic extract along with solvent derived fractions were tested in vitro against Plasmodium falciparum CQ sensitive (3D7) and resistant (K1) strains, where all the fractions exhibited potential activity (IC50 values <10µg/mL) against both the strains. Interestingly, under in vivo conditions against P. berghei in Swiss mice, preferential chemo-suppression was recorded for crude hydro-ethanolic extract (77.38%) and ethyl acetate fraction (86.09%) at the dose of 500mg/kg body weight. Additionally, ethyl acetate fraction was found to be capable of normalizing the host altered pharmacological parameters and enhanced oxidative stress augmented during the infection. The bioactivity guided fractionation lead to the isolation of bergenin as a major and active constituent (IC50, 8.07±2.05µM) of ethyl acetate fraction with the inhibition of heme polymerization pathway of malaria parasite being one of the possible chemotherapeutic target. Furthermore, bergenin exhibited a moderate antimalarial activity against P. berghei and also ameliorated parasite induced systemic inflammation in host (mice). Safe toxicity profile elucidated through in vitro cytotoxicity and in silico ADME/T predications evidently suggest that bergenin possess drug like properties. Hence, the present study validates the traditional usage of F. indica as an antimalarial remedy and also insists for further chemical modifications of bergenin to obtain more effective antimalarial chemotypes.

Guava fruit extract and its triterpene constituents have osteoanabolic effect: Stimulation of osteoblast differentiation by activation of mitochondrial respiration via the Wnt/ß-catenin signaling.

The aim of this study was to evaluate the skeletal effect of guava triterpene-enriched extract (GE) in rats and identify osteogenic compounds thereof, and determine their modes of action. In growing female rats, GE at 250 mg/kg dose increased parameters of peak bone mass including femur length, bone mineral density (BMD) and biomechanical strength, suggesting that GE promoted modeling-directed bone growth. GE also stimulated bone regeneration at the site of bone injury. In adult osteopenic rats (osteopenia induced by ovariectomy, OVX) GE completely restored the lost bones at both axial and appendicular sites, suggesting a strong osteoanabolic effect. Serum metabolomics studies showed changes in several metabolites (some of which are related to bone metabolism) in OVX compared with ovary-intact control and GE treatment to OVX rats reversed those. Out of six abundantly present triterpenes in GE, ursolic acid (UA) and 2α-hydroxy ursolic acid (2α-UA) induced osteogenic differentiation in vitro as did GE by activating Wnt/ß-catenin pathway assessed by phosphorylation of GSK-3ß. Over-expressing of constitutively active GSK-3ß (caGSK-3ß) in osteoblasts abolished the differentiation-promoting effect of GE, UA and 2α-UA. All three increased both glycolysis and mitochondrial respiration but only rotenone (inhibitor of mitochondrial electron transfer) and not 2-deoxyglucose (to block glycolysis) inhibited osteoblast differentiation. In addition, caGSK-3ß over-expression attenuated the enhanced mitochondrial respiration caused by GE, UA and 2α-UA. We conclude that GE has osteoanabolic effect which is contributed by UA and 2α-UA, and involve activation of canonical Wnt signaling which in turn modulates cellular energy metabolism leading to osteoblast differentiation.

Velvet bean severe mosaic virus: a distinct begomovirus species causing severe mosaic in Mucuna pruriens (L.) DC.

Velvet bean [Mucuna pruriens (L.) DC] is one of the most important medicinal plants. It is used to treat many ailments, but is widely used for the treatment especially for Parkinson's disease because of the presence of 3,4-dihydroxyphenylalanine (L-dopa) in it. It was noticed in last 5 years that the plants in the field showed severe mosaic, downward curling of the leaves, stunting, etc. This is consistently observed over the years in India. The disease was transmitted by whiteflies and by grafting and the causal agent was found to be a bipartite begomovirus. The whole genome was amplified by rolling circle amplification (RCA) using ϕ-29 DNA polymerase and characterized. DNA-A and DNA-B shared a 124-nucleotide (nt) long highly conserved (98%) common region (CR). Comparisons with other begomovirus showed that DNA-A sequence has highest identity (76%) with an isolate of Mungbean yellow mosaic India virus (MYMIV; AY937195) reported from India. This data suggested that the present isolate is a new species of genus Begomovirus for which the name "Velvet bean severe mosaic virus" (VbSMV) is proposed. DNA-B has a maximum sequence identity of 49% with an isolate of Horsegram yellow mosaic virus (HgYMV; AM932426) reported from India. Infectious clones consisting of a 1.7 mer partial tandem repeat of DNA-A and a dimer of DNB-B were constructed and agro-inoculated to Macuna pruriens (L.) DC plants, which showed field observed symptoms 24 days post-infiltration (dpi). In phylogenetic analysis, DNA-A and DNA-B of the present isolate grouped with DNA-A of different begomoviruses reported from fabaceous crops. The study presents first ever molecular evidence of any disease in velvet bean and whole genome analysis of the causative virus which is a distinct bipartite species of Begomovirus.