Ruchi Badoni Semwal

Efficacy and safety of Stephania glabra: an alkaloid-rich traditional medicinal plant

Stephania glabra (Roxb.) Miers (Menispermaceae) has long been used for the treatment of asthma, tuberculosis, dysentery, hyperglycaemia, cancer, fever, intestinal complaints, sleep disturbances and inflammation in many Asian countries. It mainly contains alkaloids and, until now, over 30 alkaloids such as bisbenzylisoquinolines, hasubanalactams, berberines and aporphines have been isolated from its tuber. Most of its traditional medicinal activities are scientifically approved by various in vitro and in vivo studies. It shows remarkable anti-psychotic, anti-diabetic, antipyretic, analgesic, antimicrobial and anti-hypertensive activities. This work includes comprehensive information on the ethnobotany, chemistry and pharmacology of S. glabra. This review also focuses on the future perspectives with main emphasis on the establishment of therapeutic index and safety index of the plant. This review concludes that S. glabra has a great potential to treat various diseases, and could be used as a source for novel healthcare products in the near future, which needs further studies.

Chemical Constituents and Biological Significance of the Genus Ilex (Aquifoliaceae)

The genus Ilex (Aquifoliaceae) was reviewed for its chemical constituents and pharmacological significance including traditional uses. The structure-activity relationship for various compounds was illustrated to understand the mechanism of a particular activity. The genus has been known for its numerous biological activities like antioxidant, antimicrobial, cytotoxic, anti-platelet aggregation, anti-inflammatory etc. Most of the plants of this genus are rich sources of triterpenoids and saponins. Besides, these plants also contain flavonoids, alkaloids, anthocyanins and other phenolics in minute quantity. The bioactive constituents or plants extracts themselves, in the form of herbal drugs from this genus, have been validated for the treatment of various diseases and these would be used as a new formulation for the novel drugs discovery in pharmaceutical industries.

Analgesic and Antipyretic Activities of Gindarudine, a Morphine Alkaloid from Stephania glabra

Gindarudine (GN), a morphine alkaloid isolated from the tubers of Stephania glabra (Menispermaceae), was evaluated for analgesic and antipyretic activities because of closely resembling structure to that of thebaine. The analgesic activity of GN was evaluated on albino mice by hot plate and tail immersion methods whereas antipyretic activity was studied on Brewers yeast-induced pyrexia rats. Fever was induced by injecting 20 ml/kg (s.c.) of 20% aqueous suspen- sion of Brewers yeast in normal saline and rectal temperature was recorded by clinical thermometer immediately before (- 18 h) and 18 h after (0 h) yeast administration. GN at doses of 100 and 150 mg/kg, p.o. showed significant analgesic ac- tivity (p<0.05) by increasing the threshold potential of pain whereas doses of 200 and 300 mg/kg exhibited significant (p<0.05) antipyretic effect by decreasing the rectal temperature of rats in 1 st , 3 rd and 5 th h after treatment. Aspirin (300 mg/kg, p.o.) and paracetamol (200 mg/kg, p.o.) were used as standard drugs for analgesic and antipyretic activities respec- tively. These findings demonstrate that GN have remarkable analgesic and anti-pyretic activities when compared with positive control and thus have great potential as a source for natural health products.

Ethnobotany, Pharmacology and Phytochemistry of the Genus Phoebe (Lauraceae)

The research on medicinal plants is gaining popularity due to their high efficacy, safety, quality and low side effects in comparison of synthetic medicines. Phoebe plants have been used in traditional medicine for curing various dis- eases worldwide. The Genus Phoebe comprises of about 200 species, distributed in Indo-Malaysia, West Europe, Tropical America and India. The phytochemical studies on the Genus Phoebe have revealed the presence of mostly alkaloids along with terpenoids, flavonoids, lignans and steroids. The members of this genus showed various activities such as antitumor, antiplasmodial, antimicrobial, antifungal, antidiabetic, muscles relaxant etc. The aim of present review is to explore the up to date knowledge concerning ethnobotany, pharmacology and phytochemistry of the Genus Phoebe.

A gastroretentive drug delivery system of lisinopril imbibed on isabgol-husk.

The gastroretentive drug delivery system is site-specific and allows the drug to remain in the stomach for a prolonged period of time so that it can be released in a controlled manner in gastrointestinal tract. The present study was carried out to develop a gastroretentive drug delivery system using isabgol as an excipient to prolong the residence time of the model drug lisinopril in the stomach. The gastroretentive ability of isabgol was increased by addition of NaHCO3 as a gas-generating agent while its mucoadhesive property was enhanced by incorporation of HPMC-K4M. The drug, NaHCO3 and HPMC-K3M were imbibed on isabgol-husk as per entrapment efficiency of the isabgol-husk. After drying, the product was filled in a hard gelatin capsule and evaluated for its buoyancy, mucoadhesive properties, swelling index and in vitro drug release. The lisinopril released through isabgol was delayed by 12 hours when compared to a preparation available on the market which released the complete drug in 0.5 hours. The drug release study of lisinopril from the formulation follows first order kinetics using a diffusion controlled mechanism. The results from the present study revealed that isabgol can be used as a potential excipient for the formulation of gastroretentive drug delivery systems in the near future.

Analgesic and Anti-Inflammatory Activities of Extracts and Fatty Acids from Celtis australis L

Context: Celtis australis L. (Ulmaceae) is a deciduous tree distributed to mountainous and sub-mountainous Himalaya. This plant has been used as traditional medicine in bone fracture, pimples, contusions, sprains and joint pains in India. Objectives: This is the first evaluation of C. australis extracts (bark and fruits) and fatty acids (fruits) for acute toxicity, analgesic, and anti-inflammatory activities. Materials and methods: The ethanol extracts of air dried stem bark and fruits were prepared at 30-50°C with 95% EtOH for 15h. The solvent was evaporated under reduced pressure and the powdery extracts so obtained were used for present study along with crude fatty acids obtained from column elution of n-C 6 H 12 -CHCl 3 (6:4) of EtOAc fruit extract. Crude extracts and fatty acids were screened for analgesic and anti-inflammatory activities by oral administration of three different doses at 100, 250 and 500 mg/kg of each text sample on Swiss albino mice and Sprague-Dawley rats, respectively. Results: All doses (i.e. 100, 250, and 500 mg/kg) of test samples were found active when compared with negative control. Crude extracts and fatty acids at higher concentration (i.e. 500 mg/kg) showed analgesic activity protection of 59.28, 63.22, and 45.79%, respectively, whereas at the same concentration, the anti-inflammatory inhibition was 44.26, 45.90, and 42.62%, respectively. Paracetamol and phenylbutazone were used as positive controls for analgesic and anti- inflammatory activities, respectively. Discussion and conclusion: Present study concludes that extracts (stem bark and fruits) and fatty acids (fruits) of C. australis have significant (p<0.05) analgesic and anti-inflammatory activities.

Combined Treatment with CCI779 and SB203580 Induces Cellular Senescence in Renal Cell Carcinoma Cell Line via p53 Pathway

BACKGROUND Renal cell carcinoma (RCC) is one of the most common neoplasms that occurs in the kidney and is marked by a unique biology, with a long history of poor response to conventional cancer treatments. In recent years, there have been significant advancements implemented to understanding the biology of RCC, which has led to the introduction of novel targeted therapies in the management of patients with metastatic disease. OBJECTIVE The present study was designed to evaluate the effects of p38 MAPK inhibitor (SB203580), alone and in combination with mTOR inhibitor (CCI779) on apoptosis and cell proliferation. METHOD Subtoxic concentrations of inhibitors were selected by MTT assay using A-498, ACHN and primary culture of RCC. RESULTS All the three types of RCC cells had almost similar response towards these inhibitors. The results revealed that 25µM of SB203580 and 20µM of CCI779 at 48 hrs decreased cell viability by 20% and 30%, respectively, whereas the combination of both inhibitors showed a maximum of 40% reduction in cell viability. CONCLUSION The study concludes that the combination of SB203580 and CCI779 inhibitors may induce cellular senescence in A-498 cells with higher potency than that of individual inhibitors.

Combination of mTOR and MAPK Inhibitors—A Potential Way to Treat Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common neoplasm that occurs in the kidney and is marked by a unique biology, with a long history of poor response to conventional cancer treatments. In the past few years, there have been significant advancements to understand the biology of RCC. This has led to the introduction of novel targeted therapies in the management of patients with metastatic disease. Patients treated with targeted therapies for RCC had shown positive impact on overall survival, however, no cure is possible and patients need to undergo treatment for long periods of time, which raises challenges to manage the associated adverse events. Moreover, many patients may not respond to it and even response may not last long enough in the responders. Many inhibitors of the Mammalian target of Rapamycin (mTOR) signaling pathway are currently being used in treatment of advanced RCC. Studies showed that inhibitions of mTOR pathways induce Mitogen-Activated Protein Kinase (MAPK) escape cell death and cells become resistant to mTOR inhibitors. Because of this, there is a need to inhibit both pathways with their inhibitors comparatively for a better outcome and treatment of patients with RCC.