Extracts of Neptunia prostrata Linn. ameliorates progression of diabetes mellitus and hyperlipidemia in animal models

Background: The herb Neptunia prostrata Linn. belonging to the family Mimosaceae has been used in folkloric medicine in the North-eastern states of India of Assam, Tripura and Meghalaya by indigenous herbal healers since time immemorial but there is a scarcity of any background study documenting its use as an antimicrobial herb. For the same, plants were collected and authenticated. Methods: Following identification of these herbs methanolic, ethanolic, pet ether and chloroform extracts were prepared using soxhlation. Acute toxicity study as per OECD guidelines 420 was assessed in wistar albino rats and in swiss albino mice (n=5) of both sexes at doses of 2000 mg/kg body weight and did not reveal any morbidity or mortality in the animals within the stipulated period. Phytochemical screening was performed on all four extracts of Neptunia prostrata. Results: Phytochemical constituents depicted presence of glycoside, flavonoids in only ethanolic, methanolic and chloroform extracts. Alkaloids were present in the chloroform extract. The antidiabetic and antihyperlipidemic activity was performed by HFD-STZ models in rats. The herbs showed antioxidant activity comparable to standard antioxidants in-vitro such as Ascorbic acid (Vitamin C) with comparable IC50 values. Conclusions: Results of the antidiabetic shows immense potential in animal models and therapeutics and the antibacterial screening suggests conspicuous and potent putative role in the therapeutics of a vast plethora bacterial infections that need to be corroborated for the expansion of future prospective in vivo studies with larger sample size

Current Status and Challenges of Herbal Drug Development and Regulatory aspect: A Global Perspective

Conventional herbal medication has picked up an gigantic sum of intrigued around the world due to their viability within the treatment of extreme illnesses from the period of antiquated civilizations. Phytomedicines are considered as a major healthcare supplier around the globe especially in rustic and farther ranges. A huge segment of individuals depends upon or accept in home grown drugs as a essential cure for different afflictions rather than manufactured drugs. Researchers are paying much attention towards herbal medicine as compared to synthetic drugs due to their severe side-effects, toxicity with less efficacy and specificity. Despite significant increase in global interest for the investigation and development of new botanical products, only few have been approved till now. Natural product medication development has significant technical and monetary hurdles, including a time-consuming formulation process, quality assurance, safety, therapeutic efficacy, promoting, and administrative issues. In order to meet these challenges, the regulatory agencies EMEA, ICH, AYUSH, DCGI, WHO, and U.S. FDA trying to bring these herbal drugs under regulatory pipeline under the NDA approval process. Moreover,  the process of drug discovery have also been revolutionized with the new advent of technologies such as the successful drug development of a novel therapeutic agent is critically relies on the process which adopts novel approaches and involves the concept of ADMET (i.e., absorption, distribution, metabolism, excretion, and toxicity) in the early stages of drug discovery along with the interaction profiles of herb-herb and herb-synthetic. In the present review, we will address the noteworthy opportunities and issues related with phyto-drug improvement in various developing and developed nations such as Europe, U.S. and India, its commercialization with regulatory guidelines and recommended potential methods to bring them up into the mainstream of modern medical practices and healthcare. &nbsp

Antisense oligonucleotides directed against insulin-like growth factor-II messenger ribonucleic acids delay the progress of rat hepatocarcinogenesis

Background: Hepatocellular carcinoma (HCC) is a multistep complex process, caused by many of genetic alteration. Insulin-like growth factors and their receptor have been widely implicated to HCC. Insulin-like growth factor-II (IGF-II) is a mitogenic polypeptide, found in various fetal and neonatal tissues of humans and rats and expresses in HCC. Here we investigated anticancer potential of phosphorothioate antisense oligonucleotides (ASOs) against three coding exons (exon-1/exon-2/exon-3) of IGF-II messenger ribonucleic acid in rat hepatocarcinogenesis model. Materials and Methods: During diethylnitrosamine and 2-acetylaminofluorene induced hepatocarcinogenesis, rats were treated with ASOs. Various biochemical and histological studies were conducted. Results: About 40% of carcinogen treated rats, which received two oligomers (against exon-1 or-3) did not show any hepatic lesion, hyperplastic nodule or tumor and remaining 60% of those rats showed lesion incidence and had about 59% and 55% reductions in the numbers of hepatic altered foci, respectively. Reductions in the total lesion-area when compared with carcinogen control rats were 64% and 53%, respectively for the animals treated with carcinogen and received the ASOs against exon-1/-3. Fluorescein isothiocyanate-labeled ASO reached in the hepatocytes in 2 h. No predominant IGF-II overexpression was observed in case of rats treated with the two ASOs. Treatment of the antisense IGF-II oligomers in carcinogen treated rats show better hepatocellular integrity along with several preneoplastic/neoplastic marker isoenzyme/enzyme modulations. Conclusions: Two of the three antisense oligomer-types effectively controlled IGF-II overexpression, causing the delay of the development and/or progress of hepatic cancer in rats

Immunotherapy as Novel Treatment of Lung Cancer: A systematic Review

Lung cancer is the top cause of cancer-related fatalities in both men and women around the world, and the second most commonly diagnosed cancer in both men and women. For many patients, traditional chemotherapy fails to give long-term benefit. Moreover, newer medicines targeting activating mutations in EGFR or ALK have shown increased response rates over chemotherapy in the minority of patients with these mutations; however, the majority of patients do not have actionable mutations and will not benefit from targeted therapies. In addition, several combinations of chemotherapeutic medicines with the angiogenesis inhibitor bevacizumab have provided only minor additional benefits. However, immunotherapy using checkpoint inhibitors has shown to have a lot of potential in the treatment of advanced NSCLC in recent trials. These new medications encourage the host immune system to recognise tumour cells as foreign invaders, halting their growth. They help alleviate immune system suppression, which allows tumour development to be tolerated. In checkpoint immunotherapy, humanised monoclonal antibodies targeting checkpoint signals such as programmed cell death receptor (PD-1) and programmed cell death ligand are employed (PD-L1). The immune system can be triggered to fight the tumour by inhibiting these receptors and signals. Immunotherapy for advanced lung cancer has created a new paradigm of therapeutic options, with increased survival and response rates and a less severe but distinct side profile when compared to chemotherapy. The PD-1 inhibitors nivolumab and pembrolizumab, as well as the PD-L1 inhibitor atezolizumab, have been approved by regulatory authorities for the treatment of advanced NSCLC. Hence, the current review article focuses on the role of immunotherapy, newer agents used for checkpoint inhibitors in lung cancer, their epidemiology, risk factors, side-effect profiles, therapeutic indications and their mechanism of action for the successful treatment of lung cancer

Antifungals and Drug Resistance

Antifungal drugs prevent topical or invasive fungal infections (mycoses) either by stopping growth of fungi (termed fungistatic) or by killing the fungal cells (termed fungicidal). Antibiotics also prevent bacterial infections through either bacteriostatic or bactericidal mechanisms. These microorganisms successfully develop resistance against conventional drugs that are designed to kill or stop them from multiplying. When a fungus no longer responds to antifungal drug treatments and continues to grow, this is known as antifungal drug resistance. Bacteria have an amazing capacity to become resistant to antibiotic action as well, and the effectiveness of the scarce antifungal arsenal is jeopardised by this antibiotic resistance, which poses a severe threat to public health

Antifungals and Drug Resistance

Antifungal drugs prevent topical or invasive fungal infections (mycoses) either by stopping growth of fungi (termed fungistatic) or by killing the fungal cells (termed fungicidal). Antibiotics also prevent bacterial infections through either bacteriostatic or bactericidal mechanisms. These microorganisms successfully develop resistance against conventional drugs that are designed to kill or stop them from multiplying. When a fungus no longer responds to antifungal drug treatments and continues to grow, this is known as antifungal drug resistance. Bacteria have an amazing capacity to become resistant to antibiotic action as well, and the effectiveness of the scarce antifungal arsenal is jeopardised by this antibiotic resistance, which poses a severe threat to public health

Antifungal Potential of Host Defense Peptide Mimetics in a Mouse Model of Disseminated Candidiasis

Invasive candidiasis caused by Candida albicans and non-albicans Candida (NAC) present a serious disease threat. Although the echinocandins are recommended as the first line of antifungal drug class, resistance to these agents is beginning to emerge, demonstrating the need for new antifungal agents. Host defense peptides (HDP) exhibit potent antifungal activity, but as drugs they are difficult to manufacture efficiently, and they are often inactivated by serum proteins. HDP mimetics are low molecular weight non-peptide compounds that can alleviate these problems and were shown to be membrane-active against C. albicans and NAC. Here, we expand upon our previous works to describe the in vitro and in vivo activity of 11 new HDP mimetics that are active against C. albicans and NAC that are both sensitive and resistant to standard antifungal drugs. These compounds exhibit minimum inhibitory/fungicidal concentration (MIC/MFC) in the µg/mL range in the presence of serum and are inhibited by divalent cations. Rapid propidium iodide influx into the yeast cells following in vitro exposure suggested that these HDP mimetics were also membrane active. The lead compounds were able to kill C. albicans in an invasive candidiasis CD-1 mouse model with some mimetic candidates decreasing kidney burden by 3–4 logs after 24 h in a dose-dependent manner. The data encouraged further development of this new anti-fungal drug class for invasive candidiasis

A Novel Immunocompetent Mouse Model for Testing Antifungal Drugs Against Invasive Candida albicans Infection

Disseminated infection by Candida species represents a common, often life-threatening condition. Increased resistance to current antifungal drugs has led to an urgent need to develop new antifungal drugs to treat this pathogen. However, in vivo screening of candidate antifungal compounds requires large numbers of animals and using immunosuppressive agents to allow for fungal dissemination. To increase the efficiency of screening, to use fewer mice, and to remove the need for immunosuppressive agents, which may interfere with the drug candidates, we tested the potential for a novel approach using in vivo imaging of a fluorescent strain of Candida albicans, in a mouse strain deficient in the host defense peptide, murine β-defensin 1 (mBD-1). We developed a strain of C. albicans that expresses red fluorescent protein (RFP), which exhibits similar infectivity to the non-fluorescent parent strain. When this strain was injected into immunocompetent mBD-1-deficient mice, we observed a non-lethal disseminated infection. Further, we could quantify its dissemination in real time, and observe the activity of an antifungal peptide mimetic drug by in vivo imaging. This novel method will allow for the rapid in vivo screening of antifungal drugs, using fewer mice, and increase the efficiency of testing new antifungal agents