A study on effects of cell phone tower-emitted non-ionizing radiations in an Allium cepa test system.

Considering enormous growth in population, technical advancement, and added reliance on electronic devices leading to adverse health effects, in situ simulations were made to evaluate effects of non-ionizing radiations emitted from three cell phone towers (T1, T2, and T3) of frequency bands (800, 1800, 2300 MHz), (900, 1800, 2300 MHz), and (1800 MHz), respectively. Five sites (S1-S5) were selected near cell phone towers exhibiting different power densities. The site with zero power density was considered as control. Effects of radiations were studied on morphology; protein content; antioxidant enzymes like ascorbate peroxidase (APX), superoxide dismutase (SOD), glutathione-S-transferase (GST), guaiacol peroxidase (POD), and glutathione reductase (GR); and genotoxicity using Allium cepa. Mean power density (µW/cm2) was recorded as 1.05, 1.18, 1.6, 2.73, and 12.9 for sites 1, 2, 3, 4, and 5, respectively. A significant change in morphology, root length, fresh weight, and dry weight in Allium cepa was observed under the exposure at different sites. Protein content of roots showed significant difference for samples at all sites while bulbs at sites S4 and S5 when compared to control. Antioxidant activity for root in terms of APX, GST, and POD showed significant changes at S4 and S5 and GR at site S5 and SOD at S1, S2, S3, S4, and S5. Similarly, bulbs showed significant changes at sites S4 and S5 for APX while at sites S3, S4, and S5 for POD and S2, S3, S4, and S5 for SOD and S5 for GR and GST. Genotoxicity study has shown induction of abnormalities at different stages of the cell cycle in Allium cepa root tips. The samples under exposure to radiation with maximum power density have shown maximum induction of oxidative stress and genotoxicity.

A review of botany, traditional applications, phytochemistry, pharmacological applications, and toxicology of Rubus ellipticus Smith fruits.

Rubus ellipticus Smith. (Family Rosaceae), often known as the yellow Himalayan raspberry (Yellow Hissar), is one of the most widely used edible fruits in Indian folk medicinal systems. The current review aims to identify the gap between research and existing applications of this fruit to help scientists explore the current trends and opportunities for future development. Fruits of R. ellipticus are the source of several classes of compounds. Fruits of R. ellipticus are also rich in nutrients such as carbohydrates, vitamins, and minerals. It has been shown to have significant medical value in a variety of studies, including as an anti-diabetic, nephroprotective, anti-inflammatory, analgesic, antipyretic, antitumor, wound healing, antifertility, oviposition deterrent, antibacterial, and antioxidant. Fruits of R. ellipticus have been the subject of several in vitro and in vivo investigations, all of which have corroborated their wide range of biological activities and demonstrated their potential for the identification of new therapeutic candidates and the development of innovative herbal food supplements. Additional mechanism-based pharmacological evaluation and clinical research should provide an adequate scientific basis for the traditional usage of R. ellipticus fruits, which is currently not sufficiently supported by the available research on its active components and molecular mechanisms.

Exploring the impact of integrated polyvagal exercises and knee reinforcement in females with grade II knee osteoarthritis: a randomized controlled trial.

This study aimed to compare the effects of knee strengthening exercises to those of polyvagal theory-based exercises combined with knee strengthening exercises on selected outcomes in women with grade II knee osteoarthritis (OA). A randomized controlled trial was conducted, in which 60 female participants diagnosed with grade II knee OA, with a mean age of 57.27 ± 7.81 years and knee pain rated between 4 and 7 on the visual analog scale (VAS), were assigned to either the knee strengthening exercise group (Group 1, n = 30) or the polyvagal theory-based exercise plus knee strengthening exercise group (Group 2, n = 30). Pre- and posttreatment assessment of outcome variables, including WOMAC scores (joint pain, joint stiffness, functional limitations, and the overall index), WHOQOL scores (overall quality of life, general health, physical, psychological, social, and environmental domains), and heart rate variability (HRV, time and frequency domains), were analyzed. Group 2 demonstrated significantly greater reductions in joint pain, stiffness, and functional limitations than Group 1 after the intervention. Group 2 presented with significantly improved WOMAC scores, indicating better overall outcomes. Group 2 showed significant improvements in the psychological and social domains regarding quality of life. There were no significant differences in the physical domain or the environmental domain. Group 2 showed a significant increase in high-frequency power (HF) and a significant decrease in the LF/HF ratio, suggesting improved autonomic regulation. A combination of polyvagal exercise and knee strengthening training resulted in superior outcomes compared to knee strengthening exercises alone in women with grade II knee OA. These findings support the potential effectiveness of incorporating polyvagal exercises as an adjunctive intervention for osteoarthritis management.

Antibacterial and antibiofilm efficacy of green synthesized ZnO nanoparticles using Saraca asoca leaves.

Biofilms are made up of bacterial colonies and their extracellular polymeric substances (EPS) matrix, which protects the bacteria from adverse environmental conditions. The increasing drug resistivity of pathogenic bacteria is becoming an emergency for developing new antibacterial agents. In this study, we have synthesized the zinc oxide nanoparticles (ZnO NPs) using the leaf extract of Saraca asoca plant, and the antibacterial and antibiofilm activity of green synthesized ZnO NPs was measured against the biofilm-producing bacteria Bacillus subtilis. The disk diffusion data reveals that the zone of inhibition (ZOI) starts at a concentration of 0.5 mg/mL and minimum inhibition concentration (100 µg/mL) and minimum bactericidal concentration (150 µg/mL) values were also evaluated for green synthesized ZnO nanomaterials. Crystal violet test and microscopic examination were used to assess the impact of produced nanoparticles on biofilm development. The findings indicated a nearly 45%, 64%, and 83% suppression of biofilm development at 0.5 × MIC, 0.75 × MIC, and 1 × MIC value, respectively. The biofilm biomass of the preformed or matured biofilms by the ZnO NPs was evaluated to be 68%, 50%, and 33% at concentrations of 0.5 × MIC, 0.75 × MIC, and 1 × MIC which was concentration-dependent. Moreover, flow cytometry results suggest damage to the bacterial cell membrane. The data indicated that the proportion of dead cells increased with NP concentration in comparison to the control. Therefore, it can be concluded that the green synthetic ZnO nanoparticles showed excellent antibacterial and antibiofilm activity against the Bacillus subtilis bacteria that produce biofilms and that they could be a promising substitute agent for the treatment of biofilms and drug-resistant bacteria.

Instrument-Assisted Soft Tissue Mobilization Technique versus Static Stretching in Patients with Pronated Dominant Foot: A Comparison in Effectiveness on Flexibility, Foot Posture, Foot Function Index, and Dynamic Balance.

BACKGROUND: Pronated foot is a deformity with various degrees of physical impact. Patients with a pronated foot experience issues such as foot pain, ankle pain, heel pain, shin splints, impaired balance, plantar fasciitis, etc. Objective: The study intended to compare the effectiveness of IASTM (instrument-assisted soft tissue mobilization) and static stretching on ankle flexibility, foot posture, foot function, and balance in patients with a flexible pronated foot. METHODS: Seventy-two participants between the ages of 18-25 years with a flexible pronated foot were included and allocated into three groups: Control, stretching, and IASTM group using single-blinded randomization. Range of motion (ROM) measuring ankle flexibility, foot posture index (FPI), foot function index (FFI), and dynamic balance was measured at baseline and after 4 weeks of intervention. Soft tissue mobilization was applied on to the IASTM group, while the stretching group was directed in static stretching of the gastrocnemius-soleus complex, tibialis anterior, and Achilles tendon in addition to the foot exercises. The control group received only foot exercises for 4 weeks. RESULTS: The result shows the significant improvement of the right dominant foot in ROM plantar flexion, (F = 3.94, p = 0.03), dorsiflexion (F = 3.15, p = 0.05), inversion (F = 8.54, p = 0.001) and eversion (F = 5.93, p = 0.005), FFI (control vs. IASTM, mean difference (MD) = 5.9, p < 0.001), FPI (right foot, control vs. IASTM MD = 0.88, p = 0.004), and in dynamic balance of the right-leg stance (anterior, pre vs. post = 88.55 ± 2.28 vs. 94.65 ± 2.28; anteromedial, pre vs. post = 80.65 ± 2.3 vs. 85.55 ± 2.93; posterior, pre vs. post = 83 ± 3.52 vs. 87 ± 2.99 and lateral, pre vs. post = 73.2 ± 5.02 vs. 78.05 ± 4.29) in the IASTM group. The FFI was increased remarkably in the stretching group as compared to the control group. CONCLUSIONS: Myofascial release technique, i.e., IASTM with foot exercises, significantly improves flexibility, foot posture, foot function, and dynamic balance as compared to stretching, making it a choice of treatment for patients with a flexible pronated foot.

Design, Synthesis, and Pharmacological Evaluation of Embelin-Aryl/alkyl Amine Hybrids as Orally Bioavailable Blood-Brain Barrier Permeable Multitargeted Agents with Therapeutic Potential in Alzheimer's Disease: Discovery of SB-1448.

The complex and multifaceted nature of Alzheimer's disease has brought about a pressing demand to develop ligands targeting multiple pathways to combat its outrageous prevalence. Embelin is a major secondary metabolite of Embelia ribes Burm f., one of the oldest herbs in Indian traditional medicine. It is a micromolar inhibitor of cholinesterases (ChEs) and ß-site amyloid precursor protein cleaving enzyme 1 (BACE-1) with poor absorption, distribution, metabolism, and excretion (ADME) properties. Herein, we synthesize a series of embelin-aryl/alkyl amine hybrids to improve its physicochemical properties and therapeutic potency against targeted enzymes. The most active derivative, 9j (SB-1448), inhibits human acetylcholinesterase (hAChE), human butyrylcholinesterase (hBChE), and human BACE-1 (hBACE-1) with IC50 values of 0.15, 1.6, and 0.6 µM, respectively. It inhibits both ChEs noncompetitively with ki values of 0.21 and 1.3 µM, respectively. It is orally bioavailable, crosses blood-brain barrier (BBB), inhibits Aß self-aggregation, possesses good ADME properties, and protects neuronal cells from scopolamine-induced cell death. The oral administration of 9j at 30 mg/kg attenuates the scopolamine-induced cognitive impairments in C57BL/6J mice.

An insight into the interaction between Argulus siamensis and Labeo rohita offers future therapeutic strategy to combat argulosis.

Aquaculture and fisheries are salient flourishing sectors in the world but their sustainability is often afflicted by several pathogenic diseases. Among all the pathogenic diseases of fish, parasitic diseases are found to be a major cause of concern. Argulosis is one of the dominant parasitic problems encountered in Indian aquaculture practices. Argulus siamensis is the most prevalent argulid species harming the Indian major carp species including Labeo rohita. The major carps respond to parasitic infestation by elevating various immune relevant genes. The therapeutic chemicals, synthetic drugs and other plant extracts have made a progress in the fight against argulosis. However, there is no effective vaccine and drugs are available for this disease. Thus, designing efficient, cost-effective and eco-friendly control and treatment strategies for argulosis is presently needed. Keeping the aforementioned facts in mind, the current review elaborated the immunological interaction between A. siamensis and L. rohita, available combat tactics, highlighted the already identified vaccine candidates to design effective control measures and illustrated the use of omics technology in future to combat argulosis.

Absorption and dissociation mediate the relationship between direct verbal suggestibility and impulsivity/compulsivity.

Direct verbal suggestibility refers to the capacity for an individual to experience perceptual, motor, affective and cognitive changes in response to verbal suggestions. Suggestibility is characterized by pronounced, yet reliable, inter-individual differences. Previous research and theoretical considerations suggest that greater impulsivity and compulsivity is associated to higher suggestibility, but the characteristics and mediating factors of this association are poorly understood. Using established psychometric measures in an online sample, we found positive correlations between the domain comprising impulsivity, compulsivity and behavioural activation, and the domain of suggestibility, dissociation and absorption. We also observed that dissociation and absorption mediated the link between suggestibility and impulsivity, and between suggestibility and behavioural activation, respectively. These results confirm the positive link between suggestibility and the impulsivity/compulsivity domain and shed new light on the characterisation of traits associated with suggestibility.

Antitumor Activity of Choerospondias axillaris Fruit Extract by Regulating the Expression of SNCAIP and SNCA on MDA-MB-231 Cells.

OBJECTIVE: Cancer is a huge problem of disease globally. Today, the percentage of people die from cancer is more than a combination of various diseases. In females, most common types of malignancies that occur are breast and cervical. The present focus has been shifted on medicinal plants as a form of therapy and there is a constant need to identify new therapeutic agents. Choerospondias axillaris (C. axillaris), an underutilized fruit, has been used in the remedy of various diseases. In the present communication, we evaluated the molecular mechanism of C. axillaris methanol extract in regulating cell death in human breast cancer cells (MDA-MB-231). METHODS: Methanol extract of C. axillaris was prepared and compounds were screened by Gas chromatography-mass spectrometry. The effect of fruit extract was determined on MDA-MB-231 cells by MTT ((3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay and to analyse the molecular mechanism of human breast cancer cells after treating with fruit extract, protein profiling study was performed by two-dimensional gel electrophoresis. RESULTS: A total 9 differentially expressed proteins were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS/MS) analysis. Among 9 identified proteins, synphilin-1 protein was found to be significantly downregulated, validated by western blot and RT-qPCR analysis. Possible interacting partners of synphilin-1 (SNCAIP) were analyzed for their possible role in cancer by the in-silico method. CONCLUSION: Our data implicate that the presence of bioactive compound(s) in C. axillaris fruits might play an important role in inhibiting the proliferation of breast carcinoma cells and Synphilin-1 protein may play a role of apoptotic function.

Phytochemicals in the Management of Arsenic Toxicity.

Arsenic toxicity is a major concern due to its deleterious consequences for human health. Rapid industrialization also has weakened the quality of the environment by introducing pollutants that may disrupt balanced ecosystems, adversely and irreversibly impacting humans, plants, and animals. Arsenic, an important toxicant among all environmental hazards, can lead to several detrimental effects on cells and organs, impacting the overall quality of life. Nevertheless, arsenic also has a rich history as a chemotherapeutic agent used in ancient days for the treatment of diseases such as malaria, cancer, plague, and syphilis when other chemotherapeutic agents were yet to be discovered. Arsenicosis-mediated disorders remain a serious problem due to the lack of effective therapeutic options. Initially, chelation therapy was used to metabolically eliminate arsenic by forming a complex, but adverse effects limited their pharmacological use. More recently, plant-based products have been found to provide significant relief from the toxic effects of arsenic poisoning. They act by different mechanisms affecting various cellular processes. Phytoconstituents such as curcumin, quercetin, diallyl trisulfide, thymoquinone, and others act via various molecular pathways, primarily by attenuating oxidative damage, membrane damage, DNA damage, and proteinopathies. Nonetheless, most of the phytochemicals reviewed here protect against the adverse effects of metal or metalloid exposure, supporting their consideration as alternatives to chelation therapy. These agents, if used prophylactically and in conjunction with other chemotherapeutic agents, may provide an effective approach for management of arsenic toxicity. In a few instances, such strategies like coadministration of phytochemicals with a known chelating agent have led to more pronounced elimination of arsenic from the body with lesser off-site adverse effects. This is possible because combination treatment ensures the use of a reduced dose of chelating agent with a phytochemical without compromising treatment. Thus, these therapies are more practical than conventional therapeutic agents in ameliorating arsenic-mediated toxicity. This review summarizes the potential of phytochemicals in alleviating arsenic toxicity on the basis of available experimental and clinical evidence.

Comparando o efeito da liberação miofascial e técnica de energia muscular no ângulo craniovertebral e cefaleia em pacientes com cefaleia tensional / Comparing the effect of myofascial release and muscle energy technique on craniovertebral angle and headache in tension-type headache patients

INTRODUÇÃO: Cefaleias tensionais podem ser induzidas pela postura da cabeça para frente, e há uma grande quantidade de evidências disponíveis para o manejo de cefaleias crônicas. Os dados corroboram uso de abordagens de terapia manual para gerenciar dores de cabeça do tipo tensional. Devido à postura anterior da cabeça, a região do músculo suboccipital torna-se curta, resultando em aumento da lordose e dor no pescoço. Pacientes com uma postura de cabeça ainda mais para frente têm um ângulo craniovertebral menor, o que, por sua vez, causa cefaleia do tipo tensional. OBJETIVO: O objetivo deste estudo é comparar os efeitos da terapia de liberação miofascial (LMF) e da técnica de energia muscular (TEM) com exercícios gerais do pescoço no ângulo crânio-vertebral e na cefaleia em pacientes com cefaleia do tipo tensional. MÉTODOS: No total, 75 indivíduos com cefaleia tensional e sensibilidade muscular suboccipital foram recrutados e randomizados cegamente em três grupos: o grupo LMF, o grupo TEM e o grupo controle (25 indivíduos em cada grupo). Um ângulo pré-crânio vertebral foi obtido por método fotográfico e um questionário de índice de incapacidade pré-cefaleia foi preenchido. O grupo LMF recebeu liberação crânio-basal na região suboccipital com exercícios de pescoço; o grupo TEM recebeu relaxamento pós-isométrico na região suboccipital com exercícios, e o grupo controle recebeu apenas exercícios por 2 semanas. Após duas semanas, o ângulo pós-craniano e o questionário de cefaleia foram coletados e medidos. RESULTADOS: O ângulo crânio-vertebral e o índice de cefaleia mostraram melhora significativa nos grupos TEM e LMF. Não houve diferença significativa quando os grupos TEM e LMF foram comparados. Quando comparados com o grupo controle, tanto o TEM quanto o LMF apresentaram aumento significativo do ângulo crânio-vertebral. Houve melhora significativa no índice de cefaleia após TEM, LMF ou exercício de rotina no pescoço. CONCLUSÃO: Comparado ao grupo controle, o LMF apresenta melhores resultados do que o TEM no ângulo crânio-vertebral e cefaleia.

INTRODUCTION: Tension headaches can be induced by forward head posture, and there is a wealth of evidence available for managing chronic headaches. The data support the use of manual therapy approaches to manage tension-type headaches. Because of the forward head posture, the suboccipital muscle region becomes short, resulting in an increase in lordosis and neck pain. Patients with an even more forward head posture have a smaller craniovertebral angle, which in turn causes tension-type headache. OBJECTIVE: This study aims to compare the effects of Myofascial release therapy (MFR) and Muscle energy technique (MET) with general neck exercises on the craniovertebral angle and headache in tension-type headache patients. METHODS: In total, 75 subjects with tension-type headache and suboccipital muscle tenderness were recruited and randomized blindly into three groups: the MFR group, the MET group, and the control group (25 subjects in each group). A pre-craniovertebral angle was taken by photographic method, and a pre-headache disability index questionnaire was filled in. The MFR group receives cranio-basal release in the suboccipital region with neck exercises, the MET group receives post­isometric relaxation in the suboccipital region with exercises, and the control group receives only exercises for two weeks. After two weeks, the postcranial angle and the headache questionnaire were taken and measured. RESULTS: Craniovertebral angle and headache index showed significant improvement in both the MET and MFR groups. There was no significant difference when MET and MFR groups were compared. When compared with the control group, both MET and MFR showed a significant increase in craniovertebral angle. There was a significant improvement in the headache index following MET, MFR, or routine neck exercise. CONCLUSION: Compared to the control group, MFR shows better results than MET on craniovertebral angle and headache.

Effect of serum vitamin D, calcium, and phosphorus on mandibular residual ridge resorption in completely edentulous participants: A clinical study.

STATEMENT OF PROBLEM: Published data regarding association between edentulous mandibular residual ridge resorption and nutritional status of geriatric patients is limited. PURPOSE: The purpose of this clinical study was to evaluate the degree of mandibular residual ridge resorption in completely edentulous participants and to investigate the role of dietary nutrients in the resorption process. MATERIAL AND METHODS: Three hundred (55% men and 45% women; aged between 35 and 85 years) completely edentulous participants with specific inclusion and exclusion criteria were enrolled for the study. A standardized panoramic radiograph was made, measurements were made digitally, and the amount of resorption was calculated using the Wical and Swoope method. The blood plasma levels of vitamin D3 were analyzed by using the direct competitive chemiluminescence immunoassay (CLIA) method, whereas the total calcium and phosphorus were determined by using spectrophotometer method. Statistical data of serum nutrient levels (calcium, phosphorus, and vitamin D3), age, sex, and residual ridge resorption were subjected to the Mann-Whitney U test, the Spearman correlation test, and a stepwise multiple linear regression analysis (α=.05). RESULTS: Calcium (P=.003) and phosphorus (P<.001) levels were significantly increased in the female participants as compared with the male participants. Vitamin D3 levels were similar in all the participants. Moreover, metabolic levels of calcium (rho=-0.09), phosphorus (rho=-0.10), and vitamin D3 (rho=-0.02) were found to be reduced with increasing age. However, male participants had increased mandibular residual ridge resorption (P<.001) with positive correlation (rho=0.06) when compared with female participants. Mandibular ridge resorption was increased with a decrease in levels of serum nutrients. CONCLUSIONS: Increased levels of mandibular residual ridge resorption were observed in participants with decreased levels of systemic biochemical parameters, including calcium, phosphorus, and vitamin D3. Moreover, male participants showed increased residual ridge resorption when compared with female participants, who showed a significantly higher level of serum nutrient levels. Serum nutrient levels decreased, whereas mandibular residual ridge resorption increased with age.

Reactivity of allyl methyl sulphide, the in-vitro metabolite of garlic, with some amino acids and with phospholipid involved in viral infections.

Garlic, as well as several natural food ingredients such as basil, ginger, turmeric, cinnamon, clove, pepper etc., has long been traditionally used as routine anti-viral and anti-bacterial remedy. Allyl methyl sulfide (AMS) is reportedly a persistent main active metabolite component of allicin after garlic ingestion accounting for at least 90% of the allicin consumed. Several studies have reported the presence of AMS in organs such as lung, kidney etc. and body fluids such as mucous, and blood-plasma. Glycoproteins of enveloped viruses are actively involved in viral pathogenesis. N-acetylneuraminic acid (sialic acid) and N-Acetylglucosamine, are some of the vital amino acids involved in several viral infections using glycoproteins via glycosylation. Simulations studies based on First-principles density functional theory show that these amino acids attach with AMS, and the reactions are thermodynamically spontaneous (ΔG and ΔS negative are at 310.15 K as well as lower and higher temperatures). Further, phospholipid phosphatidylethanolamine (a component of some viral envelops) also attaches readily with AMS and the reaction is spontaneous. AMS molecules attachment with viral phospholipids and amino-acids involved in viral infection would denature the virus and prevent its attachment to the host cell.Communicated by Ramaswamy H. Sarma.

Glabridin attenuates paracetamol-induced liver injury in mice via CYP2E1-mediated inhibition of oxidative stress.

CYP2E1 plays a crucial role in the bio-activation of toxic substances leading to liver damage. In this context, CYP2E1 converts paracetamol (PCM) to N-acetyl-p-benzoquinone imine (NAPQI), which is prone to cause hepatotoxicity. Hence, we aimed to explore the protective effect of glabridin on widely used PCM-induced liver injury model in the present study and, after that, correlated with the role of CYP2E1 toward its efficacy. Glabridin was isolated from Glycyrrhiza glabra and characterized before the investigation in an in-vivo mice model of PCM-induced liver injury. Glabridin after oral treatment at 5-20 mg/kg showed a considerable improvement in serum biochemical parameters (ALT and AST) and oxidative stress markers (MDA, GSH, SOD, and catalase) in comparison to only PCM-treatment. Histopathological examination of the liver depicted that glabridin exhibited substantial protection from PCM-induced liver injury compared to the disease control group. Significant down-regulation of CYP2E1 protein and its mRNA expression levels were observed in the glabridin-treated groups compared to PCM-induced respective elevation of CYP2E1. Moreover, activation of NF-κB was significantly inhibited by glabridin. Therefore, glabridin has the potential to protect PCM-induced liver injury through CYP2E1 inhibition-mediated normalization of oxidative stress. Further research is warranted to establish glabridin as a phytotherapeutics for liver protection for which no effective and safe oral drug is available to date.

Natural Products in Mitigation of SARS CoV Infections.

Severe acute respiratory syndrome (SARS) is a critical respiratory disease caused by coronaviruses (CoV). The available antiviral agents or host-specific antiinflammatory therapies are the principal treatment modalities, with drug-repurposing as the most viable approach to timely tackle the CoV pandemic. Though these approaches are successful to some extent in reducing the mortality rate, however, it is too far to see a complete escape from the current SARS CoV-2 pandemic. Plants are the primary source of diet, dietary supplements, botanical drugs, and natural products (NPs). It has been well accepted and proved via several scientific studies that plant-based therapies play a vital role in managing such infections. The faulty immune system (compromised innate immunity or aberrant immune activation) determines the severity of the respiratory distress in CoV-2 infected patients. Natural products intervene at various stages of the virus replication cycle, including inhibition of virus entry into the host cells, inhibition of serine/ cysteine proteases, RNA-dependent RNA polymerase (RdRp) or helicase. Besides, several natural products or plant-based dietary supplements have a unique ability to strengthen the immune system or alleviate the hyper-inflammatory condition. Many plant-based formulations, dietary supplements, and NPs are being investigated in clinical trials in CoV-2 infected patients, and few have already shown positive results. The review has unearthed several NP leads for medicinal chemistry programs as well as some having direct opportunity of repurposing in SARS CoV infections.

Effect of Natural Phenolics on Pharmacokinetic Modulation of Bedaquiline in Rat to Assess the Likelihood of Potential Food-Drug Interaction.

Bedaquiline (TMC-207) is a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB). Moreover, there is a present and growing concern for natural-product-mediated drug interaction, as these are inadvertently taken by patients as a dietary supplement, food additive, and medicine. In the present study, we investigated the impact of 20 plant-based natural products, typically phenolics, on in vivo oral bedaquiline pharmacokinetics, as previous studies are lacking. Three natural phenolics were identified that can significantly enhance the oral exposure of bedaquiline upon coadministration. We further investigated the possible role of all of the phytochemicals on in vitro P-glycoprotein (P-gp) induction and inhibition and CYP3A4 inhibition in a single platform as bedaquiline is the substrate for both P-gp and CYP3A4. In conclusion, curcumin, CC-I (3',5-dihydroxyflavone-7-O-ß-d-galacturonide-4'-O-ß-d-glucopyranoside), and 6-gingerol should not be coadministered with bedaquiline to avoid untoward drug interactions and, subsequently, its dose-dependent adverse effects.

Evaluation of Anti-inflammatory Effects of Choerospondias axillaris Fruit's Methanolic Extract in Synoviocytes and CIA Rat Model.

BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune, systemic disease mainly affecting joints. Presently, there is no specific treatment/ drug available for curing RA except few supportive medicines. Therefore, the focus has been shifted to medicinal plants for the treatment of such diseases. Choerospondias axillaris commonly known as Lupsi/Lapsi and has been reported to have several properties for the treatment of various diseases. OBJECTIVE: The present study has been conducted to explore the anti-inflammatory effects of Choerospondias axillaris fruit extract on Synoviocytes (FLS) and Collagen-Induced Arthritis (CIA) rat model. METHODS: Methanolic extract of the Choerospondias axillaris fruit was used for determining phytochemical, antioxidant and anti-inflammatory properties. Antioxidant activity of Choerospondias axillaris fruit was determined by free radicals scavenging assays and bioactive compounds were identified via LC-MS/MS analysis. Anti-inflammatory effect was investigated in RA and Osteo Arthritis (OA) primary cells and also in Collagen Induced Arthritis (CIA) rat models. Further, the medicinal properties of anti-inflammatory bioactive compounds were supported by docking studies. RESULTS: In-vitro and in-vivo studies showed significant decrease in the levels of inflammatory cytokines. Docking analysis revealed that quercetin inhibits TNF-α having -9.1 kcal/mol binding energy and 10.13 µM inhibitory constant. Quercetin also inhibits IL-6 having -6.6 kcal/mol binding energy and 21.9 µM inhibitory constant. CONCLUSION: Observed results suggest that the underutilized fruit Choerospondias axillaris can be used to reduce the inflammation of inflammatory diseases like RA.

Evaluation of Milk Colostrum Derived Lactoferrin of Sahiwal (Bos indicus) and Karan Fries (Cross-Bred) Cows for Its Anti-Cancerous Potential.

Lactoferrin (Lf) is an iron-binding glycoprotein protein known to have immune-modulatory role and recently, its anticancerous effect against different cancer cell types was emphasized. In the present investigation, a comparative evaluation of anticancer potential of colostrum-derived lactoferrin from Indian native zebu cow (Sahiwal, SAC), crossbred (Karan Fries, KFC) and commercially available (C-Lf) lactoferrin from exotic cow using cellular models was made. A protocol was standardized successfully to purify Lf protein from colostrum of both breeds using HPLC and purity was confirmed by LC-MS. A standardized dose of 750 µg/mL Lf was used to treat two cell types MDA-MB-231 and MCF-7 with Lf from three different sources; SAC-Lf, KFC-Lf and C-Lf for 48 h and 72 h. Different cellular parameters including cytotoxicity, viability, apoptosis and cell proliferation were determined. Comparatively, Lf from commercial source (C-Lf) had maximum effect in both cell types followed by SAC-Lf and KFC-Lf. Further, transcriptional changes in genes associated with apoptosis (Bax and Bcl-2), tumor progression (p53, p21, CD44 and NF-κß) and survival (survivin) were evaluated in Lf treatment. The overall results strongly emphasized to the fact that Lf purified from cow colostrum has the capacity to inhibit the in vitro growth of cancerous cell lines albeit to a varied extent.

Identification of embelin, a 3-undecyl-1,4-benzoquinone from Embelia ribes as a multitargeted anti-Alzheimer agent.

Beta-secreatse (BACE-1) and cholinesterases are clinically validated targets of Alzheimer's disease (AD), for which natural products have provided immense contribution. The multifaceted nature of AD signifies the need of multitargeted agents to tackle this disease. In the search of new natural products as dual BACE-1/cholinesterase inhibitors, a library of pure natural products was screened for inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE-1. The screening efforts have identified 1,4-benzoquinone "embelin," a natural product derived from Embelia ribes displaying inhibition of all three enzymes, with IC50 values of 2.5, 5.4, and 2.1 µM, respectively. This screen has also identified isoquinoline alkaloids papaverine and L-tetrahydropalmatine as AChE inhibitors. Kinetic study has shown that embelin inhibits EeAChE and EqBChE with ki values of 4.59 and 0.57 µM, in an uncompetitive and noncompetitive manner, respectively. The interactions of embelin with allosteric peripheral anionic site of cholinesterases, has further supported the results of kinetic study. Embelin has also enhanced the activity of P-gp in LS-180 cells, the efflux pump which is involved in the clearance of amyloid-ß from AD brain. Further, the cell viability study in neuronal cell line has indicated the excellent therapeutic window of embelin. These results are indicative of the fact that embelin is a multitargeted agent playing role in stopping the formation of amyloid-ß oligomers (via inhibition of BACE-1), improves cholinergic-transmission (via inhibition of AChE/BChE) and increases amyloid-ß clearance (via P-gp induction).