Phytochemical profile, antioxidant, cytotoxic and anti-inflammatory activities of stem bark extract and fractions of Ailanthus excelsa Roxb.: In vitro, in vivo and in silico approaches.

This study aimed to assess the phytochemical composition, in vitro antioxidant, cytotoxicity, and in vivo anti-inflammatory activities of the methanolic extract of Ailanthus excelsa (Simaroubaceae) stem bark and its fractions. Quantitative phytochemical analysis revealed that methanolic extract and all fractions contained a high level of flavonoids (20.40-22.91 mg/g QE), phenolics (1.72-7.41 mg/g GAE), saponins (33.28-51.87 mg/g DE), and alkaloids (0.21-0.33 mg/g AE). The antioxidant potential was evaluated in vitro using a range of assays, i.e., DPPH•, ABTS radical scavenging ability, and total antioxidant capacity. The chloroform and ethyl acetate fractions showed stronger antioxidant activity than the methanol extract. In vitro cytotoxic activity was investigated in three human tumor cell lines (A-549, MCF7 and HepG2) using the SRB assay. In addition, the in vivo anti-inflammatory effect was assessed by carrageenan-induced paw edema in rats. The chloroform fraction showed a more pronounced effect by effectively controlling the growth with the lowest GI50 and TGI concentrations. The human lung cancer cell line (A-549) was found to be more sensitive to the chloroform fraction. Furthermore, the chloroform fraction exhibited significant anti-inflammatory activity at a dose of 200 mg/kg in the latter phase of inflammation. Besides, methanol extract and ethyl acetate fraction revealed a significant cytotoxic and anti-inflammatory effects. The chloroform fraction of stem bark showed a strong anti-inflammatory effect in experimental animals and significant COX-2 inhibitory potential in the in vitro experiments. GC-MS analysis of chloroform fraction identified the phytochemicals like caftaric acid, 3,4-dihydroxy phenylacetic acid, arachidonic acid, cinnamic acid, 3-hydroxyphenylvaleric acid, caffeic acid, hexadeconoic acid, and oleanolic acid. The in-silico results suggest that identified compounds have better affinity towards the selected targets, viz. the BAX protein (PDB ID: 1F16), p53-binding protein Mdm-2 (PDB ID: 1YCR), and topoisomerase II (PDB ID: 1QZR). Amongst all, caftaric acid exhibited the best binding affinity for all three targets. Thus, it can be concluded that caftaric acid in combination with other phenolic compounds, might be responsible for the studied activity. Additional in vivo and in vitro studies are required to establish their exact molecular mechanisms and consider them as lead molecules in developing of valuable drugs for treating oxidative stress-induced disorders, cancers, and inflammations.

Phytochemical and pharmacological validation of folklore medicine practiced in south-western Satpuda Ranges (India) for management of inflammatory conditions.

INTRODUCTION: The ethnobotanical survey of the South-western Satpuda ranges has continued for decades. However, very few disease-specific surveys and their pharmacological validation have been published. The present study aimed to identify, document, and pharmacologically validate the tribal knowledge on anti-inflammatory medicinal plants. METHODS: The field survey was conducted over a year from July 2015 to June 2016, scattered in the South-Western region of Satpuda Ranges. Documentation and identification of the medicinal herbs used often in the treatment of inflammatory conditions. Two plants, namely Eulophia herbacea Lindl., and Grewia flavescens A. Juss. were commonly used for inflammatory conditions. Phytopharmacological validation was done using carrageenan induced inflammation and CFA-induced arthritis. RESULTS: The current investigation identified 32 plants from 22 different families as anti-inflammatory plants. G. flavescens exhibited substantial antiarthritic action in complete Freund's adjuvant-induced arthritis in rats, and E. herbacea showed powerful anti-inflammatory activity in carrageenan-induced rat paw edema model. This activity might be attributed to the presence of gallic acid, quercetin, ß-sitosterol and lupeol. CONCLUSION: The research reveals that selected plants had anti-inflammatory properties in both acute and chronic inflammation. Further studies to highlight the exact mechanism of action of these plants are warranted.

Role of Pentacyclic Triterpenoids in Chemoprevention and Anticancer Treatment: An Overview on Targets and Underling Mechanisms.

The incidences of cancer are continuously increasing worldwide, affecting life of millions of people. Several factors associated with the internal and external environment are responsible for this deadly disease. The key internal determinants like abnormal hormonal regulation, genetic mutations and external determinants such as lifestyle and occupational factors enhances onset of cancer. From the ancient time, plants were remained as the most trusted source of medicine for the treatment of diverse disease conditions. Extensive studies have been performed for the discovery of effective anticancer agent from the plant and still it is going on. Pentacyclic triterpenoids are biologically active phytochemicals having a different range of activities such as anti-inflammatory, hepatoprotective, anti-hypertensive, antiulcerogenic and anti-tumor. These compounds generally contain ursane, oleanane, lupane and friedelane as a chief skeleton of pentacyclic triterpenoids which are generally present in higher plants. Isoprene unit, phytochemical, with good antitumor/anticancer activity is required for the biosynthesis of pentacyclic triterpenoids. Mechanisms such as cytotoxicity, DNA polymerase inhibition, regulation of apoptosis, change in signal transductions, interfere with angiogenesis and dedifferentiation, antiproliferative activity and metastasis inhibition are might be responsible for their anticancer effect. Present review spotlights diverse targets, mechanisms and pathways of pentacyclic triterpenoids responsible for anticancer effect.

In silico PASS analysis and determination of antimycobacterial, antifungal, and antioxidant efficacies of maslinic acid in an extract rich in pentacyclic triterpenoids.

OBJECTIVE/BACKGROUND: Microbial infections such as tuberculosis is a major cause of mortality worldwide. Plant-derived phytochemicals have a long history of providing much-needed novel therapeutics. Triterpenoids are among the prominent phytochemicals that possess numerous biological activities. Among them is maslinic acid (MA), a biologically active olean-type pentacyclic triterpenoid. In search of a novel antimicrobial agent, we aimed to evaluate the antimicrobial potential of MA. METHODS: Antibacterial and antifungal activity was evaluated through the agar well diffusion method. Antitubercular activity was analysed through the agar well diffusion and disc diffusion methods, respectively. Antioxidant capacity was determined through assays for total antioxidant capacity, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, hydrogen peroxide radical scavenging, and Fe3+ reducing power. The program Prediction of Activity Spectra for Substances was used to calculate the possible biological activity of MA. RESULTS: MA showed dose-dependent antioxidant activity similar to that of ascorbic acid. It had no inhibitory effect on bacterial strains, but it had moderate activity against the fungi Aspergillus flavus and Ustilago maydis, with Aspergillus niger being the most sensitive to MA. MA also exhibited strong antimycobacterial activity. Probable antioxidant, antibacterial, and antifungal activity of MA based on software calculations are 0.479, 0.363 and 0.589 respectively. CONCLUSION: This work provides scientific evidence of the antioxidant, antifungal, and antimycobacterial activities of MA, showing its potential application in the development of natural antioxidants and antimicrobial agents for the agro-food and pharmaceutical industries.

Helicobacter pylori and cardiovascular complications: a mechanism based review on role of Helicobacter pylori in cardiovascular diseases.

Heart disease comprises a wide class of cardiovascular abnormalities, including ischemic heart disease, myocardial infarction, atherosclerosis, and coronary artery disease. It is the leading cause of death all over the world. Several traditional and novel risk factors, such as infectious and noninfectious agents, have been associated with heart disease. Out of these, Helicobacter pylori has been recently introduced as an important etiological factor for heart disease. Numerous seroepidemiological findings observed H. pylori antibodies in the blood of a patient with cardiovascular complications. The bacteria survive in the epithelial cells of gastric organs and cause digestive complications. Excess inflammatory pathogenesis and prognosis stimulate an immune response that further causes significant disturbances in various factors like cytokines, fibrinogen, triglycerides, high density lipoprotein, C-reactive protein, heat shock protein, and white blood cell count, and provoke a number of problems such as atherosclerosis and prothrombic state, and cross-reactivity which eventually leads to heart diseases. H. pylori releases toxigenic nutrients, chiefly vacuolating cytotoxin gen A (Vac A) and cytotoxin associated gene A (Cag A), of which Cag A is more virulent and involved in the formation of cholesterol patches in arteries, induction of autoimmune disorder, and release of immune mediated response. Although numerous mechanisms have been correlated with H. pylori and heart disease, the exact role of bacteria is still ambiguous.

Annona reticulata Linn. (Bullock's heart): Plant profile, phytochemistry and pharmacological properties.

From the beginning of human civilization plants and plant based chemicals are the most important sources of medicines. Phytochemical and different products obtained from plant are used as medicines, pharmaceuticals, cosmetics and food supplements. Annona reticulata Linn. ( niú xin guǒ; Bullock's heart) is a versatile tree and its fruits are edible. Parts of A. reticulata are used as source of medicine and also for industrial products. It possesses several medicinal properties such as anthelmintic, analgesic, anti-inflammatory, antipyretic, wound healing and cytotoxic effects. It is widely distributed with phytochemicals like tannins, alkaloids, phenols, glycosides, flavonoids and steroids. Present article is an attempt to highlight over taxonomy, morphology, geographical distribution, phytoconstituents and pharmacological activities of A. reticulata reported so far.

Therapeutic approaches to drug targets in atherosclerosis.

Non-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPARα, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis.

Evaluation of anthelmintic activity and in silico PASS assisted prediction of Cordia dichotoma (Forst.) root extract.

BACKGROUND: Worm infection and associated complications are severe problems that afflict a large population worldwide. Failure of synthetic drugs in worm infections because of drug resistance has made alternative drug therapy desirable. Cordia dichotoma (Forst.) is an ethnomedicinal plant which is rich in several secondary metabolites. Traditionally, the plant has been claimed to have high medicinal properties including antimicrobial activity and cytotoxicity. MATERIALS AND METHODS: The study begun with an aim to explore plant-based natural anthelmintic agents against Pheretima posthuma, an Indian earthworm. Methanol extract of the drug was obtained by successive soxhlet extraction. The extract was tested for different phytochemicals. Worms were exposed to 10 mg/ml, 25 mg/ml, 50 mg/ml, and 75 mg/ml concentrations of extract and standard drug, albendazole. A software-based tool, prediction of activity spectra for substances was used to estimate anthelmintic efficacy of plant metabolites. RESULT: The phytochemical analysis revealed presence of alkaloids, tannins, glycosides, saponins, flavonoids, and phenols. The extract showed dose-dependent effects, affecting worm motility, viability, and mortality. It was also found that the biological activity spectrum of the plant phytoconstituents such as octacosanol, lupeol, caffeic acid, and hentricontanol were >0.5 (probable activity > 0.5). CONCLUSION: The findings of the present work suggest that the extract of C. dichotoma significantly interferes with motility pattern of P. posthuma. The paralysis and mortality of P. posthuma might be due to the combined effects different phytoconstituents. The extract of C. dichotoma promises natural sources to control worm infection.

Plant profile, phytochemistry and pharmacology of Cordia dichotoma (Indian cherry): a review.

More than half of the world's population relies on the traditional medicine and major role of the traditional medicine including the use of plant extract and their active constituents. Among them, Cordia dichotoma Forst., a small to moderate size plant of family Boragenaceae, commonly called bhokar, lasura, gonda, Indian cherry and shlesmataka. Plant parts such as leaves, fruit, bark and seed have been reported for possessing antidiabetic, antiulcer, anti-inflammatory, immune-modulator and analgesic activity. Screening of fruit, leaves and seed shows the presence of pyrrolizidine alkaloids, coumarins, flavonoids, saponins, terpenes and sterols. Present review focuses on details of geographical distribution, physicochemical parameters, phytoconstituents and pharmacological properties of Cordia dichotoma reported so far.