A Review on Protease Inhibitors of Herbal Origin to Combat Malignancy.

Protease is the enzyme accountable for the breakdown of proteins i.e., proteolysis. Proteases are reportedly involved in the events of growth, development, progression and metastasis of cancers. If any agent could inhibit/retard the protease enzyme, i.e., protease inhibitor, it would arrest the cancer; thus indicating the significance of exploring protease inhibitors for latest anti-malignant drug discovery. Higher plants are the rich sources of different protease inhibitors that are effective against several types of malignancies both at preclinical and clinical stages. Natural protease inhibitors of herbal origin have both cancer chemopreventive and chemotherapeutic properties together with inhibitory activity against different types of pertinent proteases. Clinically, these herbal agents are found to be safe unlike the synthetic antineoplastic agents. Further studies in this direction are necessary in pursuit of newer generation drugs without adverse reactions for the prevention and treatment of malignancies.

An Insight into the Salutary Prospect of the Probiotic Microorganisms for the Remediation of Mercury Toxicity.

Heavy metal toxicity imposes a potential worldwide threat to environment and humans. Mercury toxicity is regarded as a serious global community health risk, as there is no particular and proven treatment for chronic mercury toxicity. Probiotics include the live apathogenic microorganisms, which are administered orally to revamp the gut microbial equilibrium thus bestowing benefit to the host. Scientific literature demonstrates different probiotic microorganisms can obviate mercurey toxicity. The present article puts together the experiments on probiotics with mercury toxicity alleviation effects in pursuit of the mechanistic hypotheses. Literature scrutiny was performed by using online bibliographic databases. Literature survey revealed that, eight types of probiotic microorganisms demonstrated significant protection from mercury toxicity in experimental pre-clinical studies. Clinical investigation with noteworthy outcome was not reported yet. Results of these studies indicate that probiotic microorganisms may hold the promise in amelioration and therapeutics of mercury toxicity. Probiotic supplementation may serve as a dietary therapeutic approach against mercurials along with extant therapies.

A Review on Experimentally Proven Medicinal Plants and Their Constituents against Fluoride Toxicity.

Fluoride toxicity, principally by polluted groundwater, is regarded as a momentous global public health risk, as there is no particular and proven treatment for chronic fluoride toxicity i.e., fluorosis which leads to several serious health complications. Scientific literature reveals several medicinal plants and natural products alleviate experimentally induced fluoride toxicity. The present review attempts to collate those experimental studies on medicinal plants and plant derived natural products with fluoride toxicity ameliorative effects. Literature scrutiny was performed by using online bibliographic databases and the studies for the last 15 years were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded. Literature study revealed that 25 medicinal plants and 17 natural products exhibited significant protection from fluoride toxicity in experimental animal models i.e., preclinical studies. Two clinical studies on medicinal plants were also found in literature showing beneficial yet poorly correlated outcome. Relevant research in this field could lead to development of a potentially useful agent in therapeutic management of fluoride toxicity in humans.

Honey Can Obviate Heavy Metal Toxicity: A Review.

Toxicity caused by heavy metals inflicts a grave global menace to the habitat and inhabitants. Arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) are the non-essential yet harmful heavy metals commonly associated with pollution and resultant health complications. Typical chelating/complexing agents are not worthy of combating heavy metal-induced sub-chronic and chronic toxicities. It transpires from scientific data mining that, honey obviates investigational heavy metal toxicity. This review aims to collate such investigations conducted against As, Cd, and Pb toxicity. There is a total of 19 pre-clinical works demonstrating the ameliorative effect of honey against empirical As, Cd, and Pb toxicity. Pre-clinical reports against Hg and clinical study against these heavy metals could not found. From the outcome of the current literature investigation, it seems that honey has a marked heavy metal toxicity meliorative effect which is chiefly ascribed to its innate antioxidant effect due to its diverse polyphenol content.

Essential Trace Metals as Countermeasure for Lead Toxicity.

Lead (Pb) is the most common toxic heavy metal that is physiologically non-essential and imposes health complications in animals and humans. Chelation therapy is considered as the definite therapy for acute lead toxicity; clinical uses of chelating agents are not recommended in long-term lead toxicity and in children. Research reveals that essential trace metals can counteract empirical Pb toxicity. This article collates the prototypical evidence of the preventive action of essential trace metals towards Pb toxicity in animals. Zinc, selenium, and their combinations are effective here. The key mechanisms of homeostasis of essential metals and cytoprotection are: modulation of signal transduction pathways of apoptosis, inflammation and immune functions (for selenium), attenuation of oxidative stress by augmenting non-enzymatic and enzymatic antioxidative systems and interference in lead accumulation in the body. By means of these mechanisms, these essential trace metals may counteract long-term lead toxicity for susceptible subjects. These mineral nutritional supplementation can easily be employed with no or less adverse effects compared to the typical chelation treatment.

Antidiabetic and antihyperlipidemic effects of Premna spinosa bark in experimental animal models.

The purpose of the study is to evaluate the antidiabetic and hyperlipidemic potential of stem bark extract of Premna spinosa (Lamiaceae), by using streptozotocin (STZ)-nicotinamide (NA)-induced diabetic and triton-induced hyperlipidemic models in albino rats. The blood glucose, total cholesterol, and triglyceride levels were determined in STZ-NA-induced diabetic and triton-induced hyperlipidemic rats, as per the respective protocols. It was found that there is the dose dependent and significant reduction in foregoing parameters on the administration of extract from Premna spinosa stem bark at the doses of 200, 400, and 800 mg/kg body weight to diabetic and hyperlipidemic rats. From these observed results it may be inferred that the stem bark of Premna spinosa possesses remarkable antidiabetic and antihyperlipidemic properties.

Protective Role of the Essential Trace Elements in the Obviation of Cadmium Toxicity: Glimpses of Mechanisms.

Cadmium (Cd) is toxic non-essential heavy metal that precipitates adverse health effects in humans and animals. Chelation therapy, the typical treatment for cadmium toxicity, has certain safety and efficacy issues to treat long term cadmium toxicity, in particular. Recent studies have shown that essential trace elements can play important roles in obviating experimental Cd toxicity. This study organizes and reviews the prototypical evidences of the protective effects of essential trace elements against Cd toxicity in animals and attempts to point out the underlying mechanisms. Zinc, selenium, iron, and combinations thereof are reported to be active. The major mechanisms elucidated inter alia are-induction of metallothionein (MT) synthesis and Cd-MT binding (for zinc), modulation of oxidative stress and apoptosis, interference in cadmium absorption and accumulation from body-thereby maintenance of essential metal homeostasis and cytoprotection. Based on the findings, essential trace elements can be recommended for the susceptible population. The application of these trace elements appears beneficial for both the prevention and remediation of long-term Cd toxicity operative via multiple mechanisms with no or minimal adverse effects as compared to the conventional chelation therapy.

Transport phenomena of Cu-S-Te chalcogenide nanocomposites: frequency response and AC conductivity.

In this work, the development and electrical characterization of several chalcogenide nanocomposites have been reported. X-ray diffraction (XRD) has been used to reveal their microstructures. Mott's variable range hopping model has been used to interpret the DC conductivity data of the nanocomposites at lower temperatures. The DC conductivity data at higher temperatures has been explained well using Greave's model. To explain the AC conductivity data, the Meyer-Neldel (MN) conduction rule has been employed. The AC conductivity spectra at different temperatures have been analyzed using Almond-West formalism. Different conduction models, namely, correlated barrier hopping (CBH) and modified non-overlapping small polaron tunneling (NSPT), have been used to interpret the conduction mechanism of the nanocomposites. Scaling of the AC conductivity spectra reveals that the electrical relaxation process is independent of temperature, but depends on the nanocomposite composition. The conductivity mechanism is explained using a schematic structural model.

The Role of Spirulina (Arthrospira) in the Mitigation of Heavy-Metal Toxicity: An Appraisal.

Heavy-metal toxicity imposes a potential worldwide threat to the environment and humans. Cadmium, mercury, lead, and arsenic are nonessential toxic heavy metals that are most frequently involved in environmental and health hazards. Conventional chelating agents are unsuitable for subchronic and chronic heavy-metal toxicities. Scientific literature reveals that Spirulina (Arthrospira), a photosynthetic filamentous cyanobacterium that is generally known as blue-green algae, alleviates experimentally induced heavy-metal toxicity. The present review attempts to summarize such studies regarding cadmium, mercury, lead, and arsenic toxicity. A total of 58 preclinical studies demonstrate the alleviative effect of Spirulina against experimental arsenic, cadmium, lead, and mercury toxicities. Five clinical studies reported protective effects of Spirulina against arsenic toxicity in humans. Clinical studies against three heavy metals were not found in the literature. The present literature study appears to show that Spirulina possesses promising heavy-metal toxicity-ameliorative effects that are mainly attributed to its intrinsic antioxidant activity.

Antidiabetic effect of Drymaria cordata leaf against streptozotocin-nicotinamide-induced diabetic albino rats.

Drymaria cordata (Caryophyllaceae), commonly known as Abhijalo in Sikkimese-Tibetan, is a creeping herb grown in tropical and subtropical regions of the world. It is used by ethnic groups of Sikkim, North-East India, for the treatment of various diseases including diabetes. This study aimed to investigate the antidiabetic effect of methanol extract from D. cordata leaf (DCME) in streptozotocin (STZ) and nicotinamide (NA)-induced type 2 diabetes in rats. Diabetic Wistar albino rats were treated with DCME at 200 mg/kg and 400 mg/kg orally for 28 days. Metformin (150 mg/kg b.w.) was used as a reference drug. Fasting blood glucose (FBG) level; serum biochemical parameters; and liver, kidney, and antioxidant parameters were estimated, and pancreatic histopathology was performed after 28 days of treatment. Administration of DCME to STZ-NA-induced diabetic rats at 200 mg/kg and 400 mg/kg orally for 28 days exhibited statistically significant (P < 0.05) and dose-dependent reduction of FBG, glycosylated hemoglobin, serum lipid, and hepatorenal antioxidative parameters in DCME-treated groups when compared to those of diabetic controls. Histopathological studies of pancreas in DCME-treated rats showed improvement in ß-cell density compared to diabetic group. The results demonstrate the significant antidiabetic potential of D. cordata leaf in albino rats plausibly by reducing oxidative stress and serum lipids levels, justifying the folkloric use of this plant in the treatment of diabetes.

The Role of Probiotics in the Amelioration of Cadmium Toxicity.

Cadmium is extremely toxic heavy metal, and there is no specific, safe, and efficacious therapeutic management of cadmium toxicity. Scientific literature reveals several probiotic microorganisms which alleviate experimentally induced cadmium toxicity in animals. The present review attempts to collate the experimental studies on probiotics and probiotic-derived natural products with cadmium toxicity ameliorative effects. Literature survey revealed that seven (7) types of probiotic microorganisms exhibited significant protection from cadmium toxicity in experimental pre-clinical studies. Clinical study with significant outcome was not found in literature. From the outcomes of the pre-clinical studies, it appears that probiotics have the prospect for alleviation and treatment of cadmium toxicity.

Probiotics against alleviation of lead toxicity: recent advances.

Lead is a toxic heavy metal and there is no specific, safe and efficacious therapeutic management of lead toxicity. Scientific literature reported that some probiotic microorganisms alleviated experimentally induced lead toxicity. The present review attempts to collate the experimental studies on probiotics with ameliorative effects. Literature survey revealed that four (4) types of probiotic microorganisms exhibited significant protection from lead toxicity in experimental pre-clinical studies. No clinical study with significant outcome was found in the literature. From the outcomes of the preclinical studies it appears that probiotics are prospective for alleviation and treatment of lead toxicity.

Medicinal plants and natural products can play a significant role in mitigation of mercury toxicity.

Mercury is a heavy metal of considerable toxicity. Scientific literature reveals various plants and plant derived natural products, i.e., phytochemicals, which can alleviate experimentally induced mercury toxicity in animals. The present review attempts to collate those experimental studies on medicinal plants and phytochemicals with ameliorative effects on mercury toxicity. A literature survey was carried out by using Google, Scholar Google, Scopus and Pub-Med. Only the scientific journal articles found in the internet for the last two decades (1998-2018) were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded. The literature survey revealed that in pre-clinical studies 27 medicinal plants and 27 natural products exhibited significant mitigation from mercury toxicity in experimental animals. Clinical investigations were not found in the literature. Admissible research in this area could lead to development of a potentially effective agent from the plant kingdom for clinical management of mercury toxicity in humans.

Medicinal plants and natural products in amelioration of arsenic toxicity: a short review.

CONTEXT: Chronic arsenic toxicity (arsenicosis) is considered a serious public health menace worldwide, as there is no specific, safe, and efficacious therapeutic management of arsenicosis. OBJECTIVES: To collate the studies on medicinal plants and natural products with arsenic toxicity ameliorative effect, active pre-clinically and/or clinically. METHODS: Literature survey was carried out by using Google, Scholar Google and Pub-Med. Only the scientific journal articles found on the internet for last two decades were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded. RESULTS: Literature study revealed that 34 medicinal plants and 14 natural products exhibited significant protection from arsenic toxicity, mostly in preclinical trials and a few in clinical studies. CONCLUSION: This research could lead to development of a potentially useful agent in clinical management of arsenicosis in humans.

Naringenin Alleviates Cadmium-Induced Toxicity through the Abrogation of Oxidative Stress in Swiss Albino Mice.

The present study evaluates the protective potential of the flavonoid naringenin (NRG) against experimentally induced cadmium (Cd) toxicity in Swiss albino mice. NRG (4 and 8 mg/kg) was orally administered to mice 30 min before oral administration of CdCl2 (12 mg/kg) for 11 consecutive days. On the 12th day, we evaluated body and organ weights, hematological profiles, serum biochemical profiles, and hepatic and renal tissue antioxidative parameters including lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase. Cotreatment with NRG markedly and significantly normalized body and organ weights, hematological profiles, and serum biochemical profiles and significantly modulated all of the hepatic and renal tissue biochemical parameters in Cd-intoxicated mice. The present findings show that NRG possesses a remarkable alleviative effect against Cd-induced toxicity in albino mice, mediated by abrogation of Cd-induced oxidative stress by multiple mechanisms.

Antitumor activity and antioxidant status of Streblus asper bark against Dalton's ascitic lymphoma in mice.

Streblus asper Lour (Moraceae), commonly known as Siamee Rough Brush in English is widely distributed in subtropical Asia and traditionally used for several medicinal purposes. In the present study, the ethyl acetate fraction of the methanol extract from Streblus asper bark (EASA) was evaluated for antitumor effect against Dalton's ascitic lymphoma (DAL) in Swiss albino mice. Twenty-four hours after intraperitoneal inoculation of DAL cells in mice, EASA was administered intraperitoneally at 200 and 400 mg/kg body weight for 9 consecutive days. On the 10th day, half of the mice were sacrificed to determine the tumor growth parameters, and the rest were kept alive for survival assessment. Hematological, serum biochemical and tissue (liver, kidney) antioxidant profiles were also determined. EASA exhibited significant and dose dependent decrease in tumor growth parameters and increased survival of DAL bearing animals. EASA significantly and dose-dependently normalized the altered hematological, serum biochemical and tissue antioxidant parameters as compared with the DAL control mice. From the present study it may be concluded that S. asper bark possesses remarkable antitumor efficacy mediated by amelioration of oxidative stress by multiple mechanisms.

ß-Carotene ameliorates arsenic-induced toxicity in albino mice.

The present study evaluated the ameliorative potential of ß-carotene (BCT) against experimentally induced arsenic toxicity in Swiss albino mice. BCT (5 and 10 mg/kg) was administered orally to mice 30 min before oral administration of arsenic trioxide (3 mg/kg) for 14 consecutive days. On 15th day, the body weights, organ weights, hematological profiles, serum biochemical profile; hepatic and renal antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase; and DNA fragmentation were evaluated. Co-treatment with BCT markedly and significantly normalized body weights, organ weights, hematological profiles, serum biochemical profile and significantly modulated all the hepatic and renal biochemical parameters and DNA fragmentation in arsenic-intoxicated mice. The present findings conclude that ß-carotene possessed remarkable ameliorative effect against arsenic-induced toxicity in albino mice mediated by its antioxidant and antigenotoxic properties.

Naringenin, a citrus flavonoid, ameliorates arsenic-induced toxicity in Swiss albino mice.

In the present study, we evaluated the ameliorative potential of a citrus flavonoid, naringenin (NRG), against experimentally induced arsenic toxicity in Swiss albino mice. NRG (5 and 10 mg kg-l) was administered orally to mice 30 minutes before oral administration of arsenic trioxide (3 mg kg-l) for 14 consecutive days. On day 15, the following parameters were evaluated: body weight; organ weight; hematological profile; serum biochemical profile; hepatic and renal tissue antioxidative parameters including lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase levels; and DNA fragmentation. Co-treatment with NRG markedly and significantly normalized body weights, organ weights, hematological profiles, and serum biochemical profiles and significantly modulated all of the hepatic and renal tissue biochemical parameters and DNA fragmentation in arsenic-intoxicated mice. The present findings indicate that naringenin remarkably ameliorated the effects of arsenic-induced toxicity in albino mice due to its strong antioxidant property.

Arsenic induced myocardial toxicity in rats: alleviative effect of Trichosanthes dioica fruit.

The present study investigated the alleviative effect of aqueous extract of Trichosanthes dioica fruit (AQTD) against arsenic induced cardiotoxicity in Wistar albino rats. AQTD (50 and 100 mg/kg) was administered orally to rats for 20 consecutive days before oral administration of sodium arsenite (10 mg/kg) for 8 days. Then the body weights, heart weights, hematological profile, serum biochemical profile; myocardial antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and DNA fragmentation were evaluated. Pretreatment with AQTD markedly and significantly normalized body weights, heart weights, hematological profile, serum biochemical profile and significantly modulated all the myocardial antioxidative parameters and reduced DNA fragmentation in arsenic intoxicated rats. Therefore, T. dioica fruit possessed remarkable alleviative effects against arsenic induced myocardial toxicity in Wistar albino rats mediated by amelioration of arsenic induced myocardial oxidative stress by several mechanisms.