Unveiling the therapeutic potential of plant steroid peimine: A study on apoptotic induction in MRMT-1 cell line-induced breast cancer in rats.

BACKGROUND: Breast cancer stands as a leading contributor to global cancer-related mortality. Progressing Research and Medical Innovations Elevate Treatment Choices and Results for Breast Cancer. Among these, Peimine, a natural steroid inherent in plants, notably within the Fritillaria species, demonstrates the capability to trigger apoptosis in breast cancer cells through the mitochondrial membrane permeation pathway. Nevertheless, its impact on an appropriate cancer model remains an area necessitating further exploration. AIM: This study explored the in vivo anticancer effects of peimine on MRMT-1 Cell-line induced breast cancer in rats. METHOD: Cancer was induced by the administration of MRMT-1 (6 x 106 cells) cells in the mammary pads of SD rats. The daily drug treatmentcommenced on day 14 and continued till 39 days. Peimine was administered in two doses (0.24 mg/kg and 0.48 mg/kg p.o) to examine its efficacy in curing breast cancer while tamoxifen was used as standard. RESULTS: A reduction in tumour size was observed in the peimine-treated groups. Peimine can correct the changed blood cell count in addition to its anti-tumour activity. In peimine-treated rats, imbalanced immune marker IgE, serum oxidative marker, and tissue apoptotic markers like cytochrome c and calcium level were shown to be restored significantly. CONCLUSION: Our findings imply that quinine has beneficial effects as an anti-neoplastic medication for breast cancer, most likely through its apoptotic activity. More research is necessary to thoroughly understand their mechanisms of action, ideal dose, and potential side effects.

Inhibiting Monoamine Oxidase in CNS and CVS would be a Promising Approach to Mitigating Cardiovascular Complications in Neurodegenerative Disorders.

The flavoenzyme monoamine oxidases (MAOs) are present in the mitochondrial outer membrane and are responsible for the metabolism of biogenic amines. MAO deamination of biological amines produces toxic byproducts such as amines, aldehydes, and hydrogen peroxide, which are significant in the pathophysiology of multiple neurodegenerative illnesses. In the cardiovascular system (CVS), these by-products target the mitochondria of cardiac cells leading to their dysfunction and producing redox imbalance in the endothelium of the blood vessels. This brings up the biological relationship between the susceptibility of getting cardiovascular disorders in neural patients. In the current scenario, MAO inhibitors are highly recommended by physicians worldwide for the therapy and management of various neurodegenerative disorders. Many interventional studies reveal the benefit of MAO inhibitors in CVS. Drug candidates who can target both the central and peripheral MAO could be a better to compensate for the cardiovascular comorbidities observed in neurodegenerative patients.

Targeting Viral ORF3a Protein: A New Approach to Mitigate COVID-19 Induced Immune Cell Apoptosis and Associated Respiratory Complications.

Infection with SARS-CoV-2 is a growing concern to the global well-being of the public at present. Different amino acid mutations alter the biological and epidemiological characteristics, as well as immune resistance of SARS-CoV-2. The virus-induced pulmonary impairment and inflammatory cytokine storm are directly related to its clinical manifestations. But, the fundamental mechanisms of inflammatory responses are found to be the reason for the death of immune cells which render the host immune system failure. Apoptosis of immune cells is one of the most common forms of programmed cell death induced by the virus for its survival and virulence property. ORF3a, a SARS-CoV-2 accessory viral protein, induces apoptosis in host cells and suppress the defense mechanism. This suggests, inhibiting SARS-CoV-2 ORF3a protein is a good therapeutic strategy for the treatment in COVID-19 infection by promoting the host immune defense mechanism.

Apoptosis promoting activity of selected plant steroid in MRMT-1 breast cancer cell line by modulating mitochondrial permeation pathway.

Escape from apoptosis is one of the main demeanor characteristics of cancer cells. Mitochondria are key players in initiating and regulating the intrinsic apoptosis pathway. Hexokinase2 (HK2) is ubiquitously expressed in several cancer cells and is essential for cell survival and death. The binding of HK2 to mitochondria promotes cell proliferation, while AKT-1 mediated pathway is crucial in this process. Peimine, a steroidal alkaloid derived from plant steroids, is screened for docking properties, ADMET properties, and drug-likeness. Apoptosis targets are predicted by network pharmacology using 47 genes associated with apoptosis. According to in silico study, peimine has the potential for dual Targeting on HK2 and AKT1. For further confirmation, peimine was subjected to Cell culture studies using MRMT-1 rat breast cancer cells. The elevated levels of cytochrome c and Caspase 9 activity indicate that the intrinsic apoptosis pathway causes cell death. The decreased glucose uptake by the MRMT-1 cells indicates that pimine inhibits glucose transport by inhibiting the membrane HK2.

Effect of Hydroaloholic Extract of Rotula Aquatica Lour on Gentamicin-Induced Nephrotoxicity in Wistar Albino Rats: An In Vitro and In Vivo Approach.

One-third of the world population suffer from kidney complications such as acute and chronic renal failure, renal calculi, kidney stones, Fanconi's syndrome and urethritis which doesn't have a proper effective treatment regimen. The current study explores the nephroprotective effect of herbal drug Rotula Aquatica by both In Vitro and In Vivo methods. MTT assay was applied In Vitro to evaluate the nephroprotective effect of R. aquatica leaves extract on HEK 293 cell line. The acute toxicity of the extract was evaluated as per the limit test under the protocol of OECD 423 at a concentration of 2000 mg/kg using 6 female rats. Further, an In Vivo study using the Gentamicin-instigated nephrotoxicity model was carried out for a period of 8 days. Biochemical markers of renal damage, endogenous antioxidants and histopathology were determined to assess the effect of treatment. The In Vitro study using HEK 293 cell line resulted in an EC50 value of 51.50 µg/ml for the extract in comparison to the standard drug Cytsone (12.26 µg/ml). Based on the limit test of OECD 423, doses of 200 and 400 mg/kg were chosen for the study. The results revealed a strong nephroprotective activity at 400 mg/kg in Gentamicin-induced nephrotoxicity against standard drug cystone by restoring the decrement in body weight, renal enzymatic and non-enzymatic antioxidants, creatinine and urea levels in urine and plasma. This indicated that hydroalcoholic extract of Rotula aquatica (HAERA) can prevent the Gentamicin toxicity due to the high content of antioxidant and anti-inflammatory secondary metabolites.

Dietary foods containing nitric oxide donors can be early curators of SARS-CoV-2 infection: A possible role in the immune system.

Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is a lethal virus that causes COVID-19 (Coronavirus disease 2019), the respiratory illness that has caused the COVID-19 pandemic. Even though multiple pharmacological trials are ongoing, there is no proof that any treatment will effectively cure or prevent COVID-19. Currently, COVID-19-infected patients are being managed with non-specific medications to suppress the symptoms and other associated co-morbidities. Nitric oxide is a bio-signaling molecule that has been shown to be effective for treating several viral infections in humans. Household Natural foods rich in nitrites and nitrates (NO donors) have been scientifically proven to have therapeutic benefits against immune-related respiratory tract infections. It was understood that NO could inhibit the early stage of SARS CoV-2 invasion into the human cell. Fruits and vegetables containing nitrites and nitrates have been revised and are now thought to be potential anti-CoV agents for effective control of other associated systemic disorders. The purpose of this review is to highlight some key facts about the treatment and prevention of COVID-19 infection with foods rich in nitric oxide and its donors. PRACTICAL APPLICATIONS: Improving the body's immune system is the early step to be considered as a preventive measure to stop the spreading of COVID-19 infection. Emerging research continues to mount that dietary nitrates/nitrites from plant foods are being healthy as well as keep us away from infectious diseases. They are now incorporated into low-risk adjuvant therapy for various infections and systemic disorders. This concept portrays the regular consuming foods such as fruits and vegetables that are rich in nitric oxide which have the potential to promote health, improve general well-being, and reduce the risk associated with the highly contagious diseases. Hence, we recommend adding nitrates and nitrites-containing food to the regular diet to improve the self-immunity as well as to fight against COVID-19 disease.

The Role of Mitochondrial Genes in Neurodegenerative Disorders.

Mitochondrial disorders are clinically heterogeneous, resulting from nuclear gene and mitochondrial mutations that disturb the mitochondrial functions and dynamics. There is a lack of evidence linking mtDNA mutations to neurodegenerative disorders, mainly due to the absence of noticeable neuropathological lesions in postmortem samples. This review describes various gene mutations in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and stroke. These abnormalities, including PINK1, Parkin, and SOD1 mutations, seem to reveal mitochondrial dysfunctions due to either mtDNA mutation or deletion, the mechanism of which remains unclear in depth.

The role of dietary polyphenols in inflammatory bowel disease: A possible clue on the molecular mechanisms involved in the prevention of immune and inflammatory reactions.

Inflammatory bowel disease (IBD) is one of the major complications of the gastrointestinal tract, characterized by chronic inflammation, which disturbs the quality of life of the affected individuals. Genetic predisposition, immune, inflammatory, and enzyme-mediated signaling cascades are the primary mechanisms involved in the pathogenesis of the disease. Currently, the treatment strategy involves the maintenance of remission and induction of inflammation by anti-inflammatory agents and immune suppressants. Polyphenol-containing diets, including fruits and vegetables of regular use, possess anti-inflammatory, and antioxidant potential through the inhibition of major contributing pathways to IBD. This review discusses the role of these dietary polyphenols in downregulating the major signaling cascades in IBD. Our review encourages the development of nutritional strategies to improve the efficiency of current therapies for IBD and reduce the risks of side effects associated with conventional therapy. PRACTICAL APPLICATIONS: At present, almost every third person in society is under stress and having chronic disorders like diabetes, arthritis, allergy, cardiovascular disease, IBD, etc. This insists on the direct/indirect role of changes in the lifestyle for such deterioration in society. This review would emphasize the medicinal value of polyphenols present in fruits and vegetables for chronic inflammatory disorders. This concept portrays the food components which have the potential to promote health, improve general well-being, and reduce the risk of IBD. We propose to add fruits with bioactive polyphenols in the regular diet to help in preventing the immune-mediated intestinal chronic inflammatory syndrome and reduce the risks of colorectal cancer development.

Antioxidant and vasorelaxant effects of aqueous extract of large cardamom in L-NAME induced hypertensive rats.

PURPOSE: The present work aimed to study the effect of aqueous extract of large cardamom (AELC) to prevent vascular remodeling and oxidative stress in Nω-Nitro-L-arginine methyl ester (L-NAME)-induced hypertension. METHOD: Male Wistar rats were administered with L-NAME 40 mg/kg/day for 28 days by oral gavage. The treatments included captopril (20 mg/kg/day) or AELC (100, 200 and 400 mg/kg/day) along with L-NAME administration. RESULTS: L-NAME treated rats showed high systolic, diastolic and mean arterial pressure, decreased nitric oxide level, increased level of malondialdehyde in plasma, heart, aorta and kidney, hypertrophy of the vascular wall and reduced vascular response to acetylcholine in phenylephrine-precontracted aorta. Treatment with AELC markedly reduced the blood pressure, restored the nitric oxide level, reduced the malondialdehyde level, alleviated the hypertrophy in L-NAME-induced hypertensive rats. Additionally, it also improved the vascular response to acetylcholine in phenylephrine pre-contracted aorta. CONCLUSION: In conclusion, our results demonstrate the preventive effect of AELC in L-NAME-induced hypertensive model, which is possibly related to antioxidant activities and restoration of nitric oxide level.

In Vitro Protective Effect of Ascorbic Acid Against Antibiotic-Induced Hepatotoxicity.

BACKGROUND: Although antibiotic-induced hepatotoxicity is recoverable with mild impairment, and some cases were reported to cause morbidity. However, an adjuvant is essential in reducing such incidences. OBJECTIVE: The aim of this study is to evaluate the protective effect of ascorbic acid on antibiotic induced liver toxicity using liver slices. METHOD: Fresh liver slices were incubated with different concentrations of sulfamethoxazole tetracycline and clavulanic acid along with ascorbic acid (200µg/ml) for 2 hours. The liver homogenate was assessed for markers like ALT, AST, MDA and CAT levels. Cytotoxicity assessment was performed using MTT assay. RESULTS: Incubating liver slices with all three antibiotics shows elevated levels of aminotransferases, MDA and CAT enzyme when compared to the control groups which indicates the level of hepatotoxicity. In the presence of ascorbic acid, the elevated levels of TBARS, ALT and AST were significantly reduced which showcases the protective effect of ascorbic acid. The percentage survival of cell was also shown to have improved while accessed using cell viability assay. CONCLUSION: Obtained data suggests that consuming vitamin C or vitamin C containing food like citrus fruits or green leafy vegetables equivalent to 3g/day during antibiotic treatment, perhaps put down the risk of liver toxicity to a greater extent.

The Benefit of Passion Fruit as an Anti-ulcerogenic Diet: Scientific Evidence by In vitro and In silico H+/K+ATPase Inhibitory Activity Assessment.

BACKGROUND: H+/K+ ATPase a protein present in the gastric parietal cells is a better target for the prevention and treatment of gastric ulcer. Plant flavonoids have been reported to elicit anti-ulcer activity by inhibiting the proton pump as well as by antioxidant defense mechanism. METHODS: Chloroform fraction of hydro-alcoholic extract of passion fruit was screened for proton pump inhibitory assay using goat parietal cell. In-silico computational docking studies were carried out using Glide program in order to validate the inhibitory action of selected constituents. RESULTS: The flavonoid rich fruit possess a promising radical scavenging activity against DPPH. 10.41µg/mL is sufficient to inhibit 50% of ATPase enzyme activity. A synergistic activity was also achieved by the fruit with sub-effective doses of lansoprazole. Fenton's oxidation induced by H2O2 was also blunted by the fruit extract. CONCLUSION: The in-vitro and in-silico findings indicated that, passion fruit can be a good dietary supplement for the prevention and management of ulcer.

Clozapine Disrupts Endothelial Nitric Oxide Signaling and Antioxidant System for its Cardiovascular Complications.

OBJECTIVE: Many drugs in current practice require additional safety labels in order to prevent potential risks to the major organ system. Psychotropic agent clozapine has been reported to produce myocarditis and other cardiac complications on repeated use. Our study aimed to establish the role of clozapine in vascular damage associated with nitric oxide metabolism. METHOD: Isolated aortic strips incubated with clozapine at different dose levels were estimated for nitrite release and antioxidant systems such as glutathione and catalase. Vascular integrity assessment was performed by recording the acetylcholine induced relaxation of phenyephrine pre-contracted aorta. RESULT: From our study, it was found that clozapine depletes the nitric oxide level in the endothelium and enhance the oxidative stress. The aorta fails to relax completely after the addition of acetylcholine indicates the deranged eNOS signaling in the endothelium. CONCLUSION: From the experimental findings, it was concluded that clozapine could depress the eNOS regulation and thereby perhaps initiates cardiovascular complications through subsequent vascular events.

Amelioration of oxidative stress by Tabernamontana divaricata on alloxan-induced diabetic rats.

OBJECTIVE: The purpose of this study was to evaluate the anti-diabetic activity of ethanol extract of Tabernamontana divaricata (L.) and its ameliorative effect on oxidative stress in alloxan-induced diabetic rats. MATERIALS AND METHODS: Diabetes was induced by single intraperitoneal injection of alloxan monohydrate (140 mg/kg body weight). Methanol extract of T. divaricata was administered at the doses of 100 and 200 mg/kg body weight in diabetic induced rats including glibenclamide (3 mg/kg) as a reference drug. In the continuous 21 days treatment, fasting blood glucose level was determined on 0, 7, 14 and 21 days. On day 21, serum lipid profiles and glycosylated hemoglobin, liver antioxidant enzymes levels were estimated. RESULTS: Experimental findings showed a significant anti-diabetic potential of the extract in terms of reduction in blood glucose levels and a correct effect on the altered biochemical parameters. Observed data were found statistically significant in correction of antioxidant enzyme level accompanied with diabetes, particularly at the dose of 200 mg/kg body weight. CONCLUSION: Based on the results, it can be concluded that the T. divaricata is found to be effective in type 2 diabetes in rats and to have an ameliorative effect on the associated oxidative stress.