Mechanisms of emerging resistance associated with non-antibiotic antimicrobial agents: a state-of-the-art review.

Although the development of resistance by microorganisms to antimicrobial drugs has been recognized as a global public health concern, the contribution of various non-antibiotic antimicrobial agents to the development of antimicrobial resistance (AMR) remains largely neglected. The present review discusses various chemical substances and factors other than typical antibiotics, such as preservatives, disinfectants, biocides, heavy metals and improper chemical sterilization that contribute to the development of AMR. Furthermore, it encompasses the mechanisms like co-resistance and co-selection, horizontal gene transfer, changes in the composition and permeability of cell membrane, efflux pumps, transposons, biofilm formation and enzymatic degradation of antimicrobial chemicals which underlie the development of resistance to various non-antibiotic antimicrobial agents. In addition, the review addresses the resistance-associated changes that develops in microorganisms due to these agents, which ultimately contribute to the development of resistance to antibiotics. In order to prevent the indiscriminate use of chemical substances and create novel therapeutic agents to halt resistance development, a more holistic scientific approach might provide diversified views on crucial factors contributing to the persistence and spread of AMR. The review illustrates the common and less explored mechanisms contributing directly or indirectly to the development of AMR by non-antimicrobial agents that are commonly used.

Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of α-Bisabolol.

α-Bisabolol is one of the important monocyclic sesquiterpenes, derived naturally from essential oils of many edible and ornamental plants. It was first obtained from Matricaria chamomilla, commonly known as chamomile or German chamomile. The available literature indicates that this plant along with other α-Bisabolol containing plants is popularly used in traditional medicine for potential health benefits and general wellbeing. Nutritional studies are indicative of the health benefits of α-Bisabolol. Numerous experimental studies demonstrated pharmacological properties of α-Bisabolol including anticancer, antinociceptive, neuroprotective, cardioprotective, and antimicrobial. This review aims to collectively present different pharmacological activities based on both in vitro and in vivo studies. In the present review using synoptic tables and figures, we comprehensively present that α-Bisabolol possesses therapeutic and protective activities, therefore, it can be used for potential health benefits based on pharmacological effects, underlying molecular mechanism, and favorable pharmaceutical properties. Based on the studies mostly performed on cell lines or animal models, it is evident that α-Bisabolol may be a promising nutraceutical and phytomedicine to target aberrant biological mechanisms which result in altered physiological processes and various ailments. Given the polypharmacological effects and pleiotropic properties, along with favorable pharmacokinetics, and dietary availability and safety, α-Bisabolol can be used as a dietary agent, nutraceutical or phytopharmaceutical agent or as an adjuvant with currently available modern medicines. The regulatory approval of this molecule for use as food additives, and in cosmetics and fragrance industry is also supportive of its human usage. Moreover, further studies are necessary to address pharmaceutical, pharmacological, and toxicological aspects before clinical or nutritional usage in humans. The biological actions and health benefits open opportunities for pharmaceutical development with pharmacological basis of its use in future therapeutics.

Pharmacological potential of JWH133, a cannabinoid type 2 receptor agonist in neurodegenerative, neurodevelopmental and neuropsychiatric diseases.

The pharmacological activation of cannabinoid type 2 receptors (CB2R) gained attention due to its ability to mitigate neuroinflammatory events without eliciting psychotropic actions, a limiting factor for the drugs targeting cannabinoid type 1 receptors (CB1R). Therefore, ligands activating CB2R are receiving enormous importance for therapeutic targeting in numerous neurological diseases including neurodegenerative, neuropsychiatric and neurodevelopmental disorders as well as traumatic injuries and neuropathic pain where neuroinflammation is a common accompaniment. Since the characterization of CB2R, many CB2R selective synthetic ligands have been developed with high selectivity and functional activity. Among numerous ligands, JWH133 has been found one of the compounds with high selectivity for CB2R. JWH133 has been reported to exhibit numerous pharmacological activities including antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, and immunomodulatory. Recent studies have shown that JWH133 possesses potent neuroprotective properties in several neurological disorders, including neuropathic pain, anxiety, epilepsy, depression, alcoholism, psychosis, stroke, and neurodegeneration. Additionally, JWH133 showed to protect neurons from oxidative damage and inflammation, promote neuronal survival and neurogenesis, and serve as an immunomodulatory agent. The present review comprehensively examined neuropharmacological activities of JWH133 in neurological disorders including neurodegenerative, neurodevelopmental and neuropsychiatric using synoptic tables and elucidated pharmacological mechanisms based on reported observations. Considering the cumulative data, JWH133 appears to be a promising CB2R agonist molecule for further evaluation and it can be a prototype agent in drug discovery and development for a unique class of agents in neurotherapeutics. Further, regulatory toxicology and pharmacokinetic studies are required to determine safety and proceed for clinical evaluation.

A focused review on CB2 receptor-selective pharmacological properties and therapeutic potential of ß-caryophyllene, a dietary cannabinoid.

The endocannabinoid system (ECS), a conserved physiological system emerged as a novel pharmacological target for its significant role and potential therapeutic benefits ranging from neurological diseases to cancer. Among both, CB1 and CB2R types, CB2R have received attention for its pharmacological effects as antioxidant, anti-inflammatory, immunomodulatory and antiapoptotic that can be achieved without causing psychotropic adverse effects through CB1R. The ligands activate CB2R are of endogenous, synthetic and plant origin. In recent years, ß-caryophyllene (BCP), a natural bicyclic sesquiterpene in cannabis as well as non-cannabis plants, has received attention due to its selective agonist property on CB2R. BCP has been well studied in a variety of pathological conditions mediating CB2R selective agonist property. The focus of the present manuscript is to represent the CB2R selective agonist mediated pharmacological mechanisms and therapeutic potential of BCP. The present narrative review summarizes insights into the CB2R-selective pharmacological properties and therapeutic potential of BCP such as cardioprotective, hepatoprotective, neuroprotective, nephroprotective, gastroprotective, chemopreventive, antioxidant, anti-inflammatory, and immunomodulator. The available evidences suggest that BCP, can be an important candidate of plant origin endowed with CB2R selective properties that may provide a pharmacological rationale for its pharmacotherapeutic application and pharmaceutical development like a drug. Additionally, given the wide availability in edible plants and dietary use, with safety, and no toxicity, BCP can be promoted as a nutraceutical and functional food for general health and well-being. Further, studies are needed to explore pharmacological and pharmaceutical opportunities for therapeutic and preventive applications of use of BCP in human diseases.

Can Echinacea be a potential candidate to target immunity, inflammation, and infection - The trinity of coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing public health emergency. The pathogenesis and complications advanced with infection mainly involve immune-inflammatory cascade. Therefore, the therapeutic strategy relies on immune modulation, reducing infectivity and inflammation. Given the interplay of infection and immune-inflammatory axis, the natural products received attention for preventive and therapeutic usage in COVID-19 due to their potent antiviral and anti-immunomodulatory activities. Recently, Echinacea preparations, particularly E. purpurea, have been suggested to be an important antiviral agent to be useful in COVID-19 by modulating virus entry, internalization and replication. In principle, the immune response and the resultant inflammatory process are important for the elimination of the infection, but may have a significant impact on SARS-CoV-2 pathogenesis and may play a role in the clinical spectrum of COVID-19. Considering the pharmacological effects, therapeutic potential, and molecular mechanisms of Echinacea, we hypothesize that it could be a reasonably possible candidate for targeting infection, immunity, and inflammation in COVID-19 with recent recognition of cannabinoid-2 (CB2) receptors and peroxisome proliferator-activated receptor gamma (PPARγ) mediated mechanisms of bioactive components that make them notable immunomodulatory, anti-inflammatory and antiviral agent. The plausible reason for our hypothesis is that the presence of numerous bioactive agents in different parts of plants that may synergistically exert polypharmacological actions in regulating immune-inflammatory axis in COVID-19. Our proposition is to scientifically contemplate the therapeutic perspective and prospect of Echinacea on infection, immunity, and inflammation with a potential in COVID-19 to limit the severity and progression of the disease. Based on the clinical usage for respiratory infections, and relative safety in humans, further studies for the evidence-based approach to COVID-19 are needed. We do hope that Echinacea could be a candidate agent for immunomodulation in the prevention and treatment of COVID-19.

Solid self-microemulsifying nutraceutical delivery system for hesperidin using quality by design: assessment of biopharmaceutical attributes and shelf-life.

AIM: The present study endeavours to develop a solid self-microemulsifying nutraceutical drug delivery system for hesperidin (HES) using quality by design (QbD) to improve its biopharmaceutical attributes. METHODS: A 32 full factorial design was employed to study the influence of factors on selected responses. Risk assessment was performed by portraying Ishikawa fishbone diagram and failure mode effect analysis (FMEA). The in vivo antidiabetic study was carried on induced diabetic rats. RESULTS: The optimised liquid SMEDDS-HES (OF) formulation showed emulsification time (Y 1) = 102.5 ± 2.52 s, globule size (Y 2) = 225.2 ± 3.40 nm, polydispersity index (Y 3) = 0.294 ± 0.62, and zeta potential (Y 4) = -25.4 ± 1.74 mV, respectively. The solid SMEDDS-HES (SOF-7) formulation was characterised by FTIR, PXRD, DSC, and SEM. The shelf life of SOF-7 was found to be 32.88 months. The heamatological and histopathological data of diabetic rats showed prominent antidiabetic activity. CONCLUSIONS: The optimised formulation showed improved dissolution, desired stability, and promising antidiabetic activity.

Plant-derived natural therapeutics targeting cannabinoid receptors in metabolic syndrome and its complications: A review.

The endocannabinoid system (ECS) is natural physiological system in the humans. The presence of the ECS system involves different roles in body. The endocannabinoid system involves regulation of most of the centers, which regulates the hunger and leads to changes in the weight. In the present article, we reviewed the role of natural cannabinoid compounds in metabolic disorders and related complications. We studied variety of a plant-derived cannabinoids in treating the metabolic syndrome including stoutness, fatty acid liver diseases, insulin obstruction, dementia, hypertension, lipid abnormalities, non-alcoholic steatohepatitis, endothelial damage, and polycystic ovarian syndrome and so on. The activation of cannabinoid receptors demonstrates a significant number of beneficial approaches concerning metabolic syndrome and reduces the pro-inflammatory cytokines on account of aggravation, decreased oxidative stress and uneasiness, diminishes liver fibrosis, with reduces adiponectin. Pre-clinical investigations of plant-derived cannabinoids resulted in promising outcomes. The different distinctive plant-derived cannabinoids were discovered like cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), and cannabidiol (CBG). It has been observed that endogenous cannabinoids and plant-derived cannabinoids have an advantageous impact on limiting the metabolic disorder arising due to lifestyle changes.

Animal Models of Inflammation for Screening of Anti-inflammatory Drugs: Implications for the Discovery and Development of Phytopharmaceuticals.

Inflammation is one of the common events in the majority of acute as well as chronic debilitating diseases and represent a chief cause of morbidity in today's era of modern lifestyle. If unchecked, inflammation leads to development of rheumatoid arthritis, diabetes, cancer, Alzheimer's disease, and atherosclerosis along with pulmonary, autoimmune and cardiovascular diseases. Inflammation involves a complex network of many mediators, a variety of cells, and execution of multiple pathways. Current therapy for inflammatory diseases is limited to the steroidal and non-steroidal anti-inflammatory agents. The chronic use of these drugs is reported to cause severe adverse effects like gastrointestinal, cardiovascular, and renal abnormalities. There is a massive need to explore new anti-inflammatory agents with selective action and lesser toxicity. Plants and isolated phytoconstituents are promising and interesting sources of new anti-inflammatories. However, drug development from natural sources has been linked with hurdles like the complex nature of extracts, difficulties in isolation of pure phytoconstituents, and the yield of isolated compounds in minute quantities that is insufficient for subsequent lead development. Although various in-vivo and in-vitro models for anti-inflammatory drug development are available, judicious selection of appropriate animal models is a vital step in the early phase of drug development. Systematic evaluation of phytoconstituents can facilitate the identification and development of potential anti-inflammatory leads from natural sources. The present review describes various techniques of anti-inflammatory drug screening with its advantages and limitations, elaboration on biological targets of phytoconstituents in inflammation and biomarkers for the prediction of adverse effects of anti-inflammatory drugs. The systematic approach proposed through present article for anti-inflammatory drug screening can rationalize the identification of novel phytoconstituents at the initial stage of drug screening programs.

Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise.

Asiatic acid (AA) is a naturally occurring aglycone of ursane type pentacyclic triterpenoids. It is abundantly present in many edible and medicinal plants including Centella asiatica that is a reputed herb in many traditional medicine formulations for wound healing and neuropsychiatric diseases. AA possesses numerous pharmacological activities such as antioxidant and anti-inflammatory and regulates apoptosis that attributes its therapeutic effects in numerous diseases. AA showed potent antihypertensive, nootropic, neuroprotective, cardioprotective, antimicrobial, and antitumor activities in preclinical studies. In various in vitro and in vivo studies, AA found to affect many enzymes, receptors, growth factors, transcription factors, apoptotic proteins, and cell signaling cascades. This review aims to represent the available reports on therapeutic potential and the underlying pharmacological and molecular mechanisms of AA. The review also also discusses the challenges and prospects on the pharmaceutical development of AA such as pharmacokinetics, physicochemical properties, analysis and structural modifications, and drug delivery. AA showed favorable pharmacokinetics and found bioavailable following oral or interaperitoneal administration. The studies demonstrate the polypharmacological properties, therapeutic potential and molecular mechanisms of AA in numerous diseases. Taken together the evidences from available studies, AA appears one of the important multitargeted polypharmacological agents of natural origin for further pharmaceutical development and clinical application. Provided the favorable pharmacokinetics, safety, and efficacy, AA can be a promising agent or adjuvant along with currently used modern medicines with a pharmacological basis of its use in therapeutics.

D-pinitol attenuates cisplatin-induced nephrotoxicity in rats: Impact on pro-inflammatory cytokines.

Cisplatin has been widely used as a first-line agent against various forms of solid cancers. However, nephrotoxicity is the major limiting factor for its clinical use. Several clinical and pre-clinical studies have suggested different strategies for the reduction of cisplatin-induced nephrotoxicity. The present study was conducted to investigate the efficacy of D-Pinitol, against cisplatin-induced nephrotoxicity in Swiss albino mice. A single intraperitoneal injection of cisplatin (20 mg/kg) was used to induce nephrotoxicity in mice. Administration of cisplatin in mice is linked with elevated oxidative stress, imbalanced biochemical parameters, apoptosis and stimulation of mitogen-activated protein kinase (MAPK) pathway. D-Pinitol is a member of the flavonoid family and a chief constituent of Sutherlandia fruitesecnce. It was administered with saline water (10, 20, 40 mg/kg, p.o.) for seven consecutive days after a single dose of cisplatin. At the end of experiment, animals were sacrificed and biochemical parameters in serum and urine were recorded. Kidneys were isolated for the estimation of tumor necrosis factor-alpha, interleukin-1ß, interlukin-6 levels and histopathological evaluations. It was noted that D-Pinitol significantly ameliorated biochemical levels of serum and urinary creatinine and blood urea nitrogen. Tissue homogenate levels of TNF-α, IL-6, IL-1ß and the renal expression of tissue nitrites were also significantly decreased in D-Pinitol treated mice. These results were supplemented by histopathological findings. This study highlights the potential role of D-Pinitol against cisplatin-induced toxicity, exhibited through favorable alterations in biochemical and histological changes as well as reduction in oxidative stress and cytokine levels.

Therapeutic Potential and Pharmaceutical Development of Thymoquinone: A Multitargeted Molecule of Natural Origin.

Thymoquinone, a monoterpene molecule is chemically known as 2-methyl-5-isopropyl-1, 4-benzoquinone. It is abundantly present in seeds of Nigella sativa L. that is popularly known as black cumin or black seed and belongs to the family Ranunculaceae. A large number of studies have revealed that thymoquinone is the major active constituent in N. sativa oil this constituent is responsible for the majority of the pharmacological properties. The beneficial organoprotective activities of thymoquinone in experimental animal models of different human diseases are attributed to the potent anti-oxidant and anti-inflammatory properties. Thymoquinone has also been shown to alter numerous molecular and signaling pathways in many inflammatory and degenerative diseases including cancer. Thymoquinone has been reported to possess potent lipophilicity and limited bioavailability and exhibits light and heat sensitivity. Altogether, these physiochemical properties encumber the successful formulation for the delivery of drug in oral dosages form and restrict the pharmaceutical development. In recent past, many efforts were undertaken to improve the bioavailability for clinical usage by manipulating the physiochemical parameters. The present review aimed to provide insights regarding the physicochemical characteristics, pharmacokinetics and the methods to promote pharmaceutical development and endorse the clinical usage of TQ in future by overcoming the associated physiochemical obstacles. It also enumerates briefly the pharmacological and molecular targets of thymoquinone as well as the pharmacological properties in various diseases and the underlying molecular mechanism. Though, a convincing number of experimental studies are available but human studies are not available with thymoquinone despite of the long history of use of black cumin in different diseases. Thus, the clinical studies including pharmacokinetic studies and regulatory toxicity studies are required to encourage the clinical development of thymoquinone.

Therapeutic Targeting of NLRP3 Inflammasomes by Natural Products and Pharmaceuticals: A Novel Mechanistic Approach for Inflammatory Diseases.

Inflammasomes are multiprotein complexes having nucleotide-binding domain and leucine-rich repeat consisting members along with pyrin and HIN domain family. An inflammasome mainly consists of cytoplasmic sensor molecule, such as NLRP3, the adaptor apoptosisassociated speck-like protein containing caspase recruitment domain) protein along with effector procaspase-1. The inflammasome regulates caspase-1 activation, resulting in secretion of interleukin- 1ß and interleukin-18. The inflammasome activation is linked with infection, stress, or other immunological signals involved in inflammation. The pathophysiological role of NLRP3 inflammasome in immune regulation, inflammatory receptor-ligand interactions, microbial-associated molecular patterns, danger as well as pathogen associated molecular patterns has been demonstrated in last few years. Furthermore, the role of the inflammasome in peripheral and central nervous system involved with cytokine and chemokine inflammatory responses has been demonstrated in preclinical and clinical studies. The understanding of molecular regulation of inflammasome associated pathways is crucial for drug design and delivery. The use of natural product as an alternate therapy is gaining focus because of easy access and cost effectiveness. A number of herbal extracts and its bioactive constituents known as phytochemicals have shown to be effective in inflammatory response mediated by NLRP3 inflammasomes pathways. To understand the interaction of phytochemicals and inflammasome at the molecular level, it is vital to develop effective drugs that can be evaluated further in the clinical settings. Therefore, this review renders an extensive account of all the phytochemicals which are evaluated either in inflammatory experimental animal models or in immortalized human/animal cell lines that modulate NLRP3 inflammasome mediated pathways to mitigate inflammatory responses with the hope that this pathway modulation by phytochemicals may provide a another class of drugs in the armamentarium as well as novel molecular mechanism of natural products targeting NLRP3 inflammasome.

Kampeferol protects against oxidative stress and apoptotic damage in experimental model of isoproterenol-induced cardiac toxicity in rats.

BACKGROUND: Myocardial infarction (MI) continues to be associated with high morbidity and mortality worldwide despite the availability of current therapeutic modalities. Kaempferol (KMP), a dietary flavonoid, possesses good antioxidant, immunomodulatory and anti-apoptotic properties and has been evaluated in the present study for its role in mitigating myocardial injury following MI. PURPOSE: In this study, the ability of KMP to protect heart against isoproterenol (ISO) induced oxidative stress and myocardial infarction was evaluated. MATERIAL AND METHODS: Male Wistar rats (n=48) were administered KMP (5, 10 & 20mg/kg/day, i.p.) or vehicle for 15 days with ISO, 85mg/kg, subcutaneously, for 2 consecutive days was also administered at 24h interval on the 13th and 14th days. On the 15th day, rats were anaesthetized and right coronary artery was cannulated to record hemodynamic parameters. Later on blood sample was collected and heart was removed to estimate biochemical, histopathological, ultrastructural and immuohistochemical studies respectively. RESULTS: ISO-treated rats showed a significant reduction in arterial pressure, maximum rate of development of left ventricular pressure and increase in left ventricular end-diastolic pressure. Also, there was a significant decrease in antioxidant enzyme levels such as superoxide dismutase, catalase and glutathione and increase in the level of malondialdehyde and serum TNF-α and IL-6 levels. In addition, the cardiac injury markers such as creatine kinase-MB and lactate dehydrogenase were increased in the serum. Furthermore, immunohistochemistry revealed an increased Bax/Bcl-2 ratio in the myocardium. KMP (5, 10 and 20mg/kg) dose dependently restored hemodynamic, left ventricular functions, decreased cardiac injury marker enzymes in serum, increased antioxidant levels, reduced lipid peroxidation and TNF-α level and apoptosis. Histopathological and ultrastructural studies support the protective effect of KMP in ISO-induced myocardial infarcted rats. CONCLUSION: Thus, the present study revealed that KMP mitigates myocardial damage in ISO-induced cardiac injury by maintaining hemodynamic and biochemical parameters and reducing inflammation owing to its anti-apoptotic, anti-inflammatory and antioxidant activities. It may be concluded that a diet containing KMP may be beneficial in those who are at the risk of myocardial injury.

Polypharmacological Properties and Therapeutic Potential of ß-Caryophyllene: A Dietary Phytocannabinoid of Pharmaceutical Promise.

BACKGROUND: ß-Caryophyllene (BCP) is a natural bicyclic sesquiterpene abundantly found in essential oils from various spices, fruits and medicinal as well as ornamental plants. It is approved by United States Food and Drug Administration and European agencies as food additive, taste enhancer and flavoring agent and termed as a phytocannabinoid. METHODS: All the available literature on BCP and its synonyms were collected through different literature databases. RESULTS: BCP was found to elicit a full agonist action on cannabinoid type 2 (CB2) receptors, a G-protein coupled receptor representing important therapeutic target in several diseases. Activation of CB2 receptors notably appeared devoid of psychotropic adverse effect of cannabinoids contrary to the CB1 receptors. In addition, it activates peroxisome proliferated activator receptors (PPARs) isoforms; PPAR-α &-γ and inhibits pathways triggered by the activation of toll like receptor complex; CD14/TLR4/MD2, reduce immuneinflammatory processes and exhibit synergy with µ-opioid receptor dependent pathways. Additionally, it found as potent antagonist of homomeric nicotinic acetylcholine receptors (α7-nAChRs) and devoid of effects mediated by serotonergic and GABAergic receptors. It also modulates numerous molecular targets by altering their gene expression, signaling pathways or through direct interaction. Various pharmacological activities such as cardioprotective, hepatoprotective, gastroprotective, neuroprotective, nephroprotective, antioxidant, anti-inflammatory, antimicrobial and immune-modulator have been reported in experimental studies. It has shown potent therapeutic promise in neuropathic pain, neurodegenerative and metabolic diseases. CONCLUSION: The present review provides a comprehensive insight of pharmacological and therapeutic potential of BCP, its molecular mechanism and signaling pathways in different pathological conditions. The review also examines the possibility of its further development as a novel candidate for various pathologies considering the polypharmacological and multifaceted therapeutic properties potential along with favorable oral bioavailability, lipophilicity and physicochemical properties.

Standardization of homeopathic mother tincture of Toxicodendron pubescens and correlation of its flavonoid markers with the biological activity.

BACKGROUND: Standardization and quality control of homeopathic drugs is very challenging. As mother tinctures are derived from complex natural resources, there is a need of systematic evaluation of chemical markers which correlate with the proposed biological activities of mother tinctures. METHODS: In present study, High-Performance Thin-Layer Chromatography (HPTLC) standardization method of homeopathic mother tinctures of Toxicodendron pubescens using quercitrin and rutin as chemical markers is validated and correlations of content of these markers with its anti-inflammatory effects are established. For HPTLC analysis, precoated silica gel plates were used as stationary phase. Two flavonoids, namely quercitrin and rutin were used as markers. Separation was achieved using methylene chloride:methanol:water:glacial acetic acid (15:1.5:1:8 v/v/v) as mobile phase. The developed plates were scanned at 365 nm. RESULTS: It was observed that quercitrin (Rf value 0.63) and Rutin (Rf value 0.41) are well resolved. The minimum detectable concentrations for quercitrin and rutin were 5 ng/spot. The linearity range was between 100 and 2000 ng/spot for both the markers. Subsequently, anti-inflammatory activity of these formulations was determined against carrageenan-induced paw edema in rats, pain threshold determined by electronic Von-Frey apparatus and paw withdrawal latency (PWL) on hot-plate. All the tested formulations of Rhus Tox showed anti-inflammatory and analgesic activity against carrageenan induced paw edema in rats. Quantitative correlation between the content of markers and anti-inflammatory activity of mother tinctures was established. RESULTS: Anti-inflammatory effect as well as effect on paw withdrawal and pain threshold, at third hour after carrageenan injection, correlated with quercitrin and rutin content in the respective formulations. CONCLUSIONS: This study validates a quantitative HPTLC method for standardization of homeopathic mother tincture of Rhus Tox and establishes quercitrin and rutin as markers corresponding its biological activity. Contents of quercitrin and rutin in T. pubescens mother tincture correlates with its anti-inflammatory and analgesic actions and the validated HPTLC method can be used in standardization of homeopathic mother tincture of T. pubescens.

Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development.

The cannabinoid molecules are derived from Cannabis sativa plant which acts on the cannabinoid receptors types 1 and 2 (CB1 and CB2) which have been explored as potential therapeutic targets for drug discovery and development. Currently, there are numerous cannabinoid based synthetic drugs used in clinical practice like the popular ones such as nabilone, dronabinol, and Δ(9)-tetrahydrocannabinol mediates its action through CB1/CB2 receptors. However, these synthetic based Cannabis derived compounds are known to exert adverse psychiatric effect and have also been exploited for drug abuse. This encourages us to find out an alternative and safe drug with the least psychiatric adverse effects. In recent years, many phytocannabinoids have been isolated from plants other than Cannabis. Several studies have shown that these phytocannabinoids show affinity, potency, selectivity, and efficacy towards cannabinoid receptors and inhibit endocannabinoid metabolizing enzymes, thus reducing hyperactivity of endocannabinoid systems. Also, these naturally derived molecules possess the least adverse effects opposed to the synthetically derived cannabinoids. Therefore, the plant based cannabinoid molecules proved to be promising and emerging therapeutic alternative. The present review provides an overview of therapeutic potential of ligands and plants modulating cannabinoid receptors that may be of interest to pharmaceutical industry in search of new and safer drug discovery and development for future therapeutics.

Protective Effects of Cardamom in Isoproterenol-Induced Myocardial Infarction in Rats.

Cardamom is a popular spice that has been commonly used in cuisines for flavor since ancient times. It has copious health benefits such as improving digestion, stimulating metabolism, and exhibits antioxidant and anti-inflammatory effects. The current study investigated the effect of cardamom on hemodynamic, biochemical, histopathological and ultrastructural changes in isoproterenol (ISO)-induced myocardial infarction. Wistar male albino rats were randomly divided and treated with extract of cardamom (100 and 200 mg/kg per oral) or normal saline for 30 days with concomitant administration of ISO (85 mg/kg, subcutaneous) on 29th and 30th days, at 24 h interval. ISO injections to rats caused cardiac dysfunction evidenced by declined arterial pressure indices, heart rate, contractility and relaxation along with increased preload. ISO also caused a significant decrease in endogenous antioxidants, superoxide dismutase, catalase, glutathione peroxidase, depletion of cardiomyocytes enzymes, creatine kinase-MB, lactate dehydrogenase and increase in lipid peroxidation. All these changes in cardiac and left ventricular function as well as endogenous antioxidants, lipid peroxidation and myocyte enzymes were ameliorated when the rats were pretreated with cardamom. Additionally, the protective effects were strengthened by improved histopathology and ultrastructural changes, which specifies the salvage of cardiomyocytes from the deleterious effects of ISO. The present study findings demonstrate that cardamom significantly protects the myocardium and exerts cardioprotective effects by free radical scavenging and antioxidant activities.