Ganoderma lucidum: Insight into antimicrobial and antioxidant properties with development of secondary metabolites.

Ganoderma lucidum is a versatile mushroom. Polysaccharides and triterpenoids are the major bioactive compounds and have been used as traditional medicinal mushrooms since ancient times. They are currently used as nutraceuticals and functional foods. G. lucidum extracts and their bioactive compounds have been used as an alternative to antioxidants and antimicrobial agents. Secondary metabolites with many medicinal properties make it a possible substitute that could be applied as immunomodulatory, anticancer, antimicrobial, anti-oxidant, anti-inflammatory, and anti-diabetic. The miraculous properties of secondary metabolites fascinate researchers for their development and production. Recent studies have paid close attention to the different physical, genetic, biochemical, and nutritional parameters that potentiate the production of secondary metabolites. This review is an effort to collect biologically active constituents from G. lucidum that reveal potential actions against diseases with the latest improvement in a novel technique to get maximum production of secondary metabolites. Studies are going ahead to determine the efficacy of numerous compounds and assess the valuable properties achieved by G. lucidum in favor of antimicrobial and antioxidant outcomes.

Knowledge, Attitudes, and Practices Related to Cervical Cancer Prevention and Screening among Female Pharmacy Students at a Public University in a Southern Region of Saudi Arabia.

Despite the availability of human papillomavirus (HPV) vaccines and screening facilities at various health centers in Saudi Arabia, the annual death rate due to cervical cancer is high. Therefore, knowledge and awareness are essential for self-care and educating others, particularly among healthcare students. The present descriptive, cross-sectional study explored female pharmacy students' knowledge, attitudes, and practices related to cervical cancer. A total of 140 students participated in the survey. The survey was conducted for the period between April 2022 to September 2023. We observed a good knowledge score and positive attitudes among 8.5% and 93.5% of participants, respectively. A total of 10% of the study participants reported good practice scores. Most participants had never been screened for cervical cancer (94.3%). Among the non-screened subjects, feeling healthy and lacking information were the participants' significant reasons for not screening for cervical cancer. A positive history of cancer related to smoking significantly impacted the knowledge score (p = 0.050). The current study reveals that healthcare awareness programs for cervical cancer and HPV vaccination are necessary at the level of educational institutions to improve public health.

Amelioration of Cancer Employing Chitosan, Its Derivatives, and Chitosan-Based Nanoparticles: Recent Updates.

The limitations associated with the conventional treatment of cancer have necessitated the design and development of novel drug delivery systems based mainly on nanotechnology. These novel drug delivery systems include various kinds of nanoparticles, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, hydrogels, and polymeric micelles. Among the various kinds of novel drug delivery systems, chitosan-based nanoparticles have attracted the attention of researchers to treat cancer. Chitosan is a polycationic polymer generated from chitin with various characteristics such as biocompatibility, biodegradability, non-toxicity, and mucoadhesiveness, making it an ideal polymer to fabricate drug delivery systems. However, chitosan is poorly soluble in water and soluble in acidic aqueous solutions. Furthermore, owing to the presence of reactive amino groups, chitosan can be chemically modified to improve its physiochemical properties. Chitosan and its modified derivatives can be employed to fabricate nanoparticles, which are used most frequently in the pharmaceutical sector due to their possession of various characteristics such as nanosize, appropriate pharmacokinetic and pharmacodynamic properties, non-immunogenicity, improved stability, and improved drug loading capacity. Furthermore, it is capable of delivering nucleic acids, chemotherapeutic medicines, and bioactives using modified chitosan. Chitosan and its modified derivative-based nanoparticles can be targeted to specific cancer sites via active and passive mechanisms. Based on chitosan drug delivery systems, many anticancer drugs now have better effectiveness, potency, cytotoxicity, or biocompatibility. The characteristics of chitosan and its chemically tailored derivatives, as well as their use in cancer therapy, will be examined in this review.

Resveratrol-Loaded Chia Seed Oil-Based Nanogel as an Anti-Inflammatory in Adjuvant-Induced Arthritis.

Natural anti-inflammatory nutraceuticals may be useful in preventing rheumatoid arthritis from worsening. Resveratrol (RV) and chia seed oil, having antioxidant potential, can assist in avoiding oxidative stress-related disorders. This investigation developed and evaluated resveratrol-loaded chia seed oil-based nanoemulsion (NE) gel formulations through in vitro and in vivo studies. The physical stability and in vitro drug permeability of the chosen formulations (NE1 to NE10) were studied. The optimized RV-loaded nanoemulsion (NE2) had droplets with an average size of 37.48 nm that were homogeneous in shape and had a zeta potential of -18 mV. RV-NE2, with a permeability of 98.21 ± 4.32 µg/cm2/h, was gelled with 1% carbopol-940P. A 28-day anti-arthritic assessment (body weight, paw edema, and levels of pro-inflammatory mediators including TNF-α, IL-6, IL-1ß, and COX-2) following topical administration of RV-NE2 gel showed significant reversal of arthritic symptoms in arthritic Wistar rats induced by Freund's complete adjuvant injection. Therefore, RV-NE2 gel demonstrated the potential to achieve local therapeutic benefits in inflammatory arthritic conditions due to its increased topical bioavailability and balancing of pro-inflammatory mediators.

Levosimendan: mechanistic insight and its diverse future aspects in cardiac care.

Inotropic agents are generally recommended to use in patients with acute decompensated heart failure (HF) with reduced ejection fraction (HFrEF) concurrent to end-organ dysfunction. However, due to certain pharmacological limitations like developing life threatening arrhythmia and tolerance, cannot be employed as much as needed. Meanwhile, Calcium ion (Ca2+) sensitisers exhibits their inotropic action by increasing the sensitivity of the cardiomyocyte to intracellular Ca2+ ion and have been reported as emerging therapeutic alternative in HF cases. Levosimendan (LEVO) is an inodilator and with its unique pharmacology justifying its use in a wide range of cardiac alterations in HF particularly in undergoing cardiac surgery. It is also reported to be better than classical inotropes in maintaining cardiac mechanical efficacy and reducing congestion in acute HF with hypotension. This review paper was designed to compile various evidence about basic pharmacology and potential clinical aspects of LEVO in cardiac surgery and other HF associated alterations. This will benefit directly to the researcher in initiating research and to fill the gaps in the area of thrust.

Preliminary investigation on impact of intergenerational treatment of resveratrol endorses the development of 'super-pups'.

BACKGROUND: Redox biology balances free radical generation and scavenging systems, whereas an imbalanced cellular redox can hasten the onset of various diseases and be regarded as a Pandora's box of ailments. The current study aims to assess the pathophysiological impact of intergenerational resveratrol treatment on diabetes-related cognitive and cardio-renal disorders. MATERIAL AND METHOD: Diabetic rats of the first, second, and third generations were subjected to an intergenerational treatment of resveratrol (20 mg/kg/p.o./day) for 5 months. During this period, the second generation of animals (pups of the first generation) was produced. After the adulthood of second-generation rats, they used to produce third-generation rats. The rats of each generation were evaluated for physiological parameters (BMI, litter size, and life expectancy) and the pathological impact of streptozotocin (55 mg/kg/i.p.), cognitive dysfunctions, and cardio-renal injury. RESULTS: The intergenerational treatment of resveratrol significantly reduced litter size and improved anthropometric parameters, life expectancy, and blood glucose levels in diabetic animals. Resveratrol treatment ameliorates oxidative stress as measured by increased serum nitrite/nitrate concentrations, SOD activity, reduced glutathione concentrations, total serum antioxidant capacity, and diminished serum TBARS level in diabetic animals. Furthermore, diabetic rats receiving intergenerational resveratrol treatment showed improved cognitive behaviour and cardio-renal functionality when compared to the disease control group. CONCLUSION: The intergenerational treatment of resveratrol improved the physiological traits and vital abilities of the heart, kidney, and brain, which endorse its antioxidant potential. Surprisingly, resveratrol treatment increases the second and third generations' resistance to neurobehavioral changes, diabetes, and -associated cardio-renal dysfunction, implying that these generations are "super-pups."

Impact of polycystic ovary syndrome on quality of life of women in correlation to age, basal metabolic index, education and marriage.

Polycystic ovary syndrome (PCOS) is the major endocrine related disorder in young age women. Physical appearance, menstrual irregularity as well as infertility are considered as a sole cause of mental distress affecting health-related quality of life (HRQOL). This prospective case-control study was conducted among 100 PCOS and 200 healthy control cases attending tertiary care set up of AIIMS, Patna during year 2017 and 2018. Pre-validated questionnaires like Short Form Health survey-36 were used for evaluating impact of PCOS in women. Multivariate analysis was applied for statistical analysis. In PCOS cases, socioeconomic status was comparable in comparison to healthy control. But, PCOS cases showed significantly decreased HRQOL. The higher age of menarche, irregular/delayed menstrual history, absence of child, were significantly altered in PCOS cases than control. Number of child, frequency of pregnancy, and miscarriage were also observed higher in PCOS cases. Furthermore, in various category of age, BMI, educational status and marital status, significant differences were observed in the different domain of SF-36 between PCOS and healthy control. Altogether, increased BMI, menstrual irregularities, educational status and marital status play a major role in altering HRQOL in PCOS cases and psychological care must be given during patient care.

Edaravone and benidipine protect myocardial damage by regulating mitochondrial stress, apoptosis signalling and cardiac biomarkers against doxorubicin-induced cardiotoxicity.

Background: Doxorubicin (DOX) is a potential chemotherapeutic agent but its use is restricted due to cardiotoxicity. Edaravone is a potent-free radical scavenging agent used in cerebral ischaemia. Benidipine is a triple calcium channel blocker.Objective: We investigated the potential cardioprotective effects of edaravone and benidipine alone and their combination against DOX-induced cardiotoxicity. Cardiotoxicity was induced by administering six equal injections of DOX (2.5 mg/kg) on alternative days for 2 weeks.Result: DOX-treated group showed significant increase level of lipid peroxide and decrease in antioxidant status along with mitochondrial enzymatic activity. Cardiotoxity effect of DOX illustrated by significantly increased the cardiac biomarkers such as Cardiac troponin-I, Brain natriuretic peptide, Creatine kinase-MB in serum. Significant increased activation of TNF-α, Caspase-3 activity and myocardial infarct size in DOX-treated group. Histopathological evaluation also confirmed the DOX-induced cardiotoxicity. Pretreated with edaravone and benidipine was significantly attenuated level of thiobarbituric acid reactive substance, endogenous enzymes, mitochondrial enzyme activities and cardiac biomarkers. Furthermore, pretreated group showed decreased activation of TNF-α, Caspase-3 activity along with reduction in the myocardial infarct size. Histopathological evaluation also strengthened the above results.Conclusion: Taken together these results suggest that the pretreated with edaravone and benidipine have potential protective effect against DOX-induced cardiotoxicity.

Pitavastatin ameliorates myocardial damage by preventing inflammation and collagen deposition via reduced free radical generation in isoproterenol-induced cardiomyopathy.

Pitavastatin inhibits 3 hydroxy 3 methyl glutaryl coenzyme A (HMGCoA) reductase enzyme, preventing cholesterol synthesis along with elevating high density apolipoprotein A1 (Apo-A1). The present study was designed to evaluate cardioprotective potential of pitavastatin at 1 mg/kg/day and 3 mg/kg/day dose for 14 days in low dose isoproterenol (ISO) (5 mg/kg/day for 7 consecutive days) induced myocardial damage. ISO administration induced significant reduction in endogenous antioxidant enzymes like reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and raised thiobarbituric acid reactive substances (TBARS) indicating activated lipid peroxidation. Along with this, a significant increase in level of cardiac injury biomarkers vie, creatine kinase (CK-MB), lactate dehydrogenase (LDH), aspartate amino transferase (AST), tumor necrosis factor (TNF-α) and transforming growth factor (TGF-ß) as well as brain natriuretic peptide (BNP). Histological examination also revealed marked myocardial tissue damage in ISO treated rats. However, pretreatment with pitavastatin (3 mg/kg/day) significantly maintained nearly normal levels of cardiac biomarkers and oxidant antioxidant status as well as lipid peroxidation in ISO induced MI rats. Cardiac histological assessment and infarct size assessment also showed marked reduction in myocardial architecture alteration including infarct size as well as collagen deposition by pitavastatin that strongly supported biochemical findings. These observations strongly corroborate that pitavastatin prevents myocardial damages via up regulation of endogenous oxidants along with its hypocholesterolemic activity.

Sacubitril and valsartan protect from experimental myocardial infarction by ameliorating oxidative damage in Wistar rats.

BACKGROUND: Sacubitril (SAC), a neprilysin inhibitor prevent degradation of neprilysin and activate cGMP signaling pathways leading to rise in blood volume concurrent to blood pressure by means of vasoactive peptides, adrenomedullin, and bradykinin. OBJECTIVE: The aim of this study was to evaluate the anti-ischemic effects of SAC through inhibiting neprilysin in isoproterenol (ISO) induced myocardial infarction (MI) in Wistar albino rats. ISO (85 mg/kg) was injected subcutaneously at the end of 14 days pre-treatment with SAC and valsartan (VAL). RESULT: Biochemical investigation revealed that SAC along with VAL significantly prevented the antioxidant enzymes (SOD, Catalase, GR, GPx, GST, and GSH) degradation and malondialdehyde (MDA) induced by ISO intoxication in Wistar rats. Along with this, cardiac biomarkers (LDH, CK-MB, ALT, AST, and ALP) were also significantly ameliorated by SACand VAL in ISO-treated rats. Concurrently, decreased infarction area (IA)and marked reduction in myofibril damage by SACand VAL further supported its protective benefits in MI. CONCLUSION: Taken together, the results suggest that inhibition of enzyme neprilysin alleviated the ISO induces myocardial damage mediated by its strong antioxidant potential.

EGFR tyrosine kinase inhibition decreases cardiac remodeling and SERCA2a/NCX1 depletion in streptozotocin induced cardiomyopathy in C57/BL6 mice.

AIM: Epidermal growth factor receptor (EGFR) related reactive oxygen species (ROS) generation results in myocardial damage. We aimed to investigate the role of gefitinib (EGFR-tyrosine kinase inhibitor) in diabetic cardiomyopathy (DbCM). METHOD: DbCM was induced by injecting streptozotocin (55 mg/kg for 5 consecutive days) to C57/BL6 mice intraperitoneally. Diabetic C57/BL6 mice (fasting blood glucose level ≥ 250 mg/dl) were allocated into four study groups and treated with two doses of gefitinib (30 mg/kg and 350 mg/kg per day) as well as ramipril (3 mg/kg/day) for four weeks. KEY FINDINGS: We observed a significant correlation between persistent hyperglycaemia with cardiac remodeling and alterations in myocardial architecture. Gefitinib significantly prevented lipid peroxidation (MDA), damage of antioxidant enzymes like superoxide dismutase (SOD), Catalase, glutathione (GSH) and thioredoxin reductase (TrxR). Gefitinib also prevented hypertrophy of myocardium evidenced by reduced heart weight to body weight ratio and TGF­ß related collagen deposition. Gefitinib maintained cardiac biomarkers like lactate dehydrogenase (LDH), Creatine Kinase­MB, brain natriuretic peptide (BNP) and cardiac Troponin­I (cTroponinI) indicating reduced myocardial damage. Decreased sarcoplasmic endoplasmic reticulum Ca2 + ATPase2a (SERCA2a) and sodium­calcium exchanger-1 (NCX1) protein depletion after gefitinib administration indicated improved Ca2+ homeostasis during myocardial contractility. Histopathology and transmission electron microscopy clearly showed almost normal myofibrils and mitochondrial arrangements in gefitinib treated mice. SIGNIFICANCE: Our findings suggest that gefitinib protects myocardial damage in DbCM via balancing oxidant-antioxidant system, decreased collagen deposition as well as improved CKMB, BNP, cTroponinI and SERCA2a/NCX-1. Thereby, it indicated that gefitinib may be a potential therapeutic drug for treating DbCM.

Synthesis of stable benzimidazole derivatives bearing pyrazole as anticancer and EGFR receptor inhibitors.

A new series of benzimidazole linked pyrazole derivatives were synthesized by cyclocondensation reaction through one-pot multicomponent reaction in absolute ethanol. All the synthesized compounds were tested for their in vitro anticancer activities on five human cancer cell lines including MCF-7, HaCaT, MDA-MB231, A549 and HepG2. EGFR receptor inhibitory activities were carried out for all the compounds. Majority of the compounds showed potent antiproliferative activity against the tested cancer cell lines. Compound 5a showed the most effective activity against the lungs cancer cell lines (IC50 = 2.2 µM) and EGFR binding (IC50 = 0.97 µM) affinity as compared to other members of the series. Compound 5a inhibited growth of A549 cancer cells by inducing a strong G2/M phase arrest. In addition, same compound inhibited growth of A549 cancer cells by inducing apoptosis. In molecular docking studies compound 5a was bound to the active pocket of the EGFR (PDB 1M17) with five key hydrogen bonds and two π-π interaction with binding energies ΔG = -34.581 Kcal/mol.

2-[(4-Chlorobenzyl) amino]-4-methyl-1,3-thiazole-5-carboxylic acid exhibits antidiabetic potential and raises insulin sensitivity via amelioration of oxidative enzymes and inflammatory cytokines in streptozotocin-induced diabetic rats.

Thiazole derivatives are potential candidates for drug development. They can be efficiently synthesized and are extremely active against several diseases, including diabetes. In our present study, we investigated the anti-diabetic, anti-oxidant and anti-inflammatory properties of 2-[(4-Chlorobenzyl) amino]-4-methyl-1,3-thiazole-5-carboxylic acid (BAC) a new thiazole derivative, in a streptozotocin (STZ) induced neonatal model of non-insulin dependent diabetes mellitus (NIDDM) rats. Diabetes was induced by injecting STZ (100mg/kg) intraperitoneally to two days old pups. BAC administration for 3 weeks significantly decreased blood glucose and raised insulin level and improves insulin sensitivity (KITT) level. Additionally, BAC also suppressed several inflammatory cytokines generation as evidenced by decreased levels of serum tumor necrosis factor-α and interleukin-6. In addition, BAC also protects against hyperlipidemia and liver injury. Furthermore, BAC significantly restored pancreatic lipid peroxidation, catalase, superoxide dismutase, and reduced glutathione content. Histological studies of pancreatic tissues showed normal architecture after BAC administration to diabetic rats. Altogether, our results suggest that BAC successfully reduces the blood glucose level and possesses anti-oxidant as well as anti-inflammatory activity. This leads to decreased histological damage in diabetic pancreatic tissues suggesting the possibility of future diabetes treatments.

Hit to lead optimization of a series of N-[4-(1,3-benzothiazol-2-yl)phenyl]acetamides as monoacylglycerol lipase inhibitors with potential anticancer activity.

A total of thirty five new N-[4-(1,3-benzothiazol-2-yl)phenyl]acetamide derivatives were synthesized and structures of all the compounds were confirmed on the basis of elemental analysis and collective use of IR, (1)H NMR, (13)C NMR and mass spectral data. Compounds were tested for their ability to inhibit human monoacylglycerol lipase (hMAGL) enzyme. Eight compounds 4, 19-21, 24-26, and 34 reduced the hMAGL activity less than 50% at 100 nM concentrations. The halogen substituted aniline derivatives 20, 21 and 24-26 were found to be most active among all the synthesized compounds having IC50 value in the range of 6.5-9 nM. Twenty five compounds were selected by NCI, USA for one dose anticancer screening. Compound 21 (NSC: 780167) and 24 (NSC: 780168) fulfilled prearranged doorstep growth inhibition criteria and further selected for NCI full panel five dose assay at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 µM). Both the compounds 21 and 24 were found to be most active against MCF7 and MDA-MB-468 breast cancer cell lines. The GI50 value of 32.5 nM (MCF7) and 23.8 nM (MDA-MB-468) was observed for compound 21. Compound 24 showed GI50 values of 37.1 nM against MCF7 breast cancer cell line and 25.1 nM against MDA-MB-468 breast cancer cell line.

Levosimendan suppresses oxidative injury, apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy.

Diabetic cardiomyopathy plays a major role in morbidity and mortality among cardiovascular disorder-related complications. This study was designed to explore long-term benefits of Levosimendan (LEVO) along with Ramipril and Insulin. Diabetic cardiomyopathy was induced using streptozotocin (STZ) at the dose of 25 mg/kg/body weight/day for three consecutive days in Wistar rats. Rats were randomly divided into 10 groups and treatments were started after 2 weeks of STZ administration. A gradual but severe hyperglycemia ((§§§)p < 0.001) was observed in all STZ-treated groups except those received insulin (2 U/day). LEVO alone and in combination with Ramipril and Insulin normalized (**p < 0.01) mean arterial pressure and heart rate, restored catalase, superoxide dismutase, malondialdehyde, glutathione level and also attenuated (***p < 0.001) the raised serum levels of creatine kinase-heart type, lactate dehydrogenase, tumor necrosis factor-alpha, C-reactive protein, and caspase-3 level in heart tissue altered after STZ treatment. Myofibril degeneration, mitochondrial fibrosis and vacuolization occurred after STZ treatment, were also reversed by LEVO in combination with Ramipril and Insulin. The combination of LEVO with Ramipril and Insulin improved hemodynamic functions, maintained cardiac enzymes and ameliorated myofibril damage in diabetic cardiomyopathy.

Edaravone protects rats against oxidative stress and apoptosis in experimentally induced myocardial infarction: Biochemical and ultrastructural evidence.

OBJECTIVES: The present study was designed to evaluate the cardioprotective potential of edaravone on oxidative stress, anti-apoptotic, anti-inflammatory and ultrastructure findings in isoproterenol (ISO) induced myocardial infarction (MI) in rats. METHODS: Rats were pretreated with edaravone (1, 3, 10 mg/kg body weight-1 day-1) intraperitoneally. MI was induced by subcutaneous administration of ISO (85 mg/kg body weight-1) at two doses with 24h interval. RESULTS: ISO treated rats showed significant increase in the levels of thiobarbituric acid reactive substances (TBARS) and decreased levels of reduced glutathione, glutathione perdoxidase, glutathione reductase and glutathione-S- transferase in the cardiac tissues. Moreover, significant increase in the levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), C--reactive protein and caspase-3 activity was observed in ISO treated group. Pretreatment of ISO intoxicated rats with edaravone showed significant decrease in the level of TBARS, increased activities of antioxidant enzymes and significantly decreased levels of LDH and CK-MB. Moreover, results also showed decreased C-reactive protein level, caspase-3 activity and maintained ultrastructure of the myocardial cells. DISCUSSION: Our study suggests that edaravone possess strong cardioprotective potential. Edaravone may have exhibited cardioprotective effects by restoring antioxidant defense mechanism, maintaining integrity of myocardial cell membrane, reducing apoptosis and inflammation against ISO induced MI and associated oxidative stress.