CETYL ALCOHOL AND OLEIC ACID SOPHOROLIPIDS EXHIBIT ANTICANCER ACTIVITY

Objective: Sophorolipids (SLs) are glycolipid biosurfactants that have been shown to have anticancer activity. We investigated the anti-cancer activity of cetyl alcohol sophorolipids (CAS) and oleic acid sophorolipids (OAS) in breast cancer (MCF-7, MDA-MB-231), cervical cancer (SiHa, HeLa) and non-cancerous (HaCaT and RAW264.7) cell lines.Methods: For cell viability assay, MCF-7, MDA-MB-231, SiHa, HeLa, HaCaT and RAW264.7 cell lines were treated with different concentrations (0-160 µg/ml) of OAS and CAS for 24h. The cell viability was determined by MTT dye uptake method. Cell proliferation assay was determined by using trypan blue dye exclusion method.Results: Our preliminary data shows that compared to OAS, CAS exhibited more significant reduction in the viability of MCF-7, MDA-MB-231 and SiHa. However, compared to CAS, OAS induced more decrease in viability in HeLa cells. Interestingly, both the types of SLs did not affect the viability of non-cancerous cells. Moreover, CAS, when used as a coating material, induced proliferation in macrophage cell line, RAW264.7.Conclusion: The present study provides an important clue towards the anti-cancer potential of OAS and CAS derived from Candida bombicola. Interestingly, the ability of CAS to promote the proliferation of non-cancerous cells suggests its future application as a scaffold for enhancing the adhesion and proliferation of normal cells.Keywords: Oleic acid sophorolipids, Cetyl alcohol sophorolipids, Breast cancer, Cervical cance

COMPARATIVE ANALYSIS OF ANTI-INFLAMMATORY ACTIVITY OF AQUEOUS AND METHANOLIC EXTRACTS OF C. CASSIA AND C. ZEYLANICUM IN RAW264.7, SW1353 AND PRIMARY CHONDROCYTES

Objectives: The objective of this research was to compare the anti-inflammatory activity of aqueous and methanolic extracts of C. cassia (CC) and C. zeylanicum (CZ) in mouse macrophage (RAW264.7) and human chondrosarcoma (SW1353) cell lines as well as in human primary chondrocytes, to correlate their efficacy in management of osteoarthritis (OA) related pathophysiology.Methods: RAW264.7, SW1353 and human primary chondrocytes were pre-treated with aqueous extracts of C. cassia (CCW) and C. zeylanicum (CZW) and methanolic extracts of C. cassia (CCM) and C. zeylanicum (CZM) at various concentrations (0.1-100 µg/ml) for 1 h, followed by stimulation with LPS and IL-1β, respectively. The effect of CCM, CCW, CZM and CZW on the production of nitric oxide (NO) was evaluated by Griess reaction. Evaluation of prostaglandin E2 (PGE2) and leukotriene (LTB4) proteins was performed by EIA-Monoclonal based kits. The effect of these extracts on matrix metalloproteinase (MMPs-2, 9 and 13) levels was analyzed by SensoLyte® fluorimetric MMP assay kit.Results: The methanolic extracts (CCM, CZM) of both the varieties of cinnamon were found to be more effective than the aqueous extracts in terms of PGE2, LTB4 and MMP inhibition.We found that in RAW 264.7, CCM and CZM decreased NO and PGE2 production by45.40%±8.6; 65.63%±5.7 and 79.88%±1.2; 95.91%±0.3, respectively. Similarly, in SW1353 and chondrocytes, CCM decreased PGE2 production by 68.8%±6.4;36.1%±9.5, respectively whereas CZM reduced PGE2 production by 70.2%±2.3; 52.3%±5.4, respectively. Moreover, in SW1353 and chondrocytes CCM decreased LTB4 production by 85.47%±3.03; 99.6%±0.2, respectively whereas CZM reduced LTB4 production by 67.5%±5.6; 75.6%±1.2, respectively. In chondrocytes both CCM and CZM significantly reduced the levels of MMP-2(55.7%±5.2; 73.1%±7.1), MMP-9 (57.5%±4.7; 74.5%±5.2) and MMP-13 (90.1%±2.6; 71.2%±12.5), respectively. However, on comparing the two species of cinnamon, C. zeylanicumwas found to be more effective than C. cassia andthus could be considered for its potential therapeutic application in the management of inflammatory conditions associated with OA.Conclusion: The present study would help in choosing better of the two species of cinnamon for their possible therapeutic application in the management of inflammatory condition associated with OA.Â

EVALUATION OF ACUTE AND SUB-ACUTE TOXICITY OF A STANDARDIZED POLYHERBAL FORMULATION (HC9): AN IN VIVO STUDY

Objective: In the present study, we have performed the acute and sub-acute toxicity of a standardized polyherbal formulation (HC9) in Swiss albino mice. Methods: In acute toxicity study, the mice were orally administered with different doses (1750 and 2000 mg/kg) of HC9 and monitored for 14 d. In the sub-acute toxicity study, animals received HC9 extract by oral gavage at the doses of 250, 500 and 1000 mg/kg/day (????=5/group/sex) for 28 d. At the end of the study, the animals were sacrificed and evaluated for effect of HC9 on biochemical, hematological and histopathological parameters. Results: HC9 did not produce any adverse effects in biochemical, hematological, urine and histopathological parameters in mice. HC9 did not induce any adverse effects in terms of mortality and clinical signs in the acute toxicity study. It was well-tolerated by mice up to 2000 mg/kg/body weight. In sub-acute toxicity study, no treatment-related adverse effects were found in the mice upto 1000 mg/kg/day dose. No significant changes were observed in biochemical and hematological parameters as well as histopathology of tissues (liver, kidney, spleen, heart, lung, thymus, adrenal gland, epididymis and testis/ovary) among mice of either sex. Conclusion: Our results showed that HC9 did not induce any acute and sub-acute toxicity in male and female mice, thereby, suggesting its safety for future clinical application

Cinnamaldehyde, cinnamic acid, and cinnamyl alcohol, the bioactives of cinnamomum cassia exhibit HDAC8 inhibitory activity : an in vitro and in silico study

BACKGROUND : The altered expression of histone deacetylase family member 8 (HDAC8) has been found to be linked with various cancers, thereby making its selective inhibition a potential strategy in cancer therapy. Recently, plant secondary metabolites, particularly phenolic compounds, have been shown to possess HDAC inhibitory activity. OBJECTIVE : In the present work, we have evaluated the ability of cinnamaldehyde (CAL), cinnamic acid (CA), and cinnamyl alcohol (CALC) (bioactives of Cinnamomum) as well as aqueous cinnamon extract (ACE), to inhibit HDAC8 activity in vitro and in silico. MATERIALS AND METHODS : HDAC8 inhibitory activity of ACE and cinnamon bioactives was determined in vitro using HDAC8 inhibitor screening kit. Trichostatin A (TSA), a well‑known anti‑cancer agent and HDAC inhibitor, was used as a positive control. In silico studies included molecular descriptor Analysis molecular docking absorption, distribution, metabolism, excretion, and toxicity prediction, density function theory calculation and synthetic accessibility program. RESULTS : Pharmacoinformatics studies implicated that ACE and its Bioactives (CAL, CA, and CALC) exhibited comparable activity with that of TSA. The highest occupied molecular orbitals and lowest unoccupied molecular orbitals along with binding energy of cinnamon bioactives were comparable with that of TSA. Molecular docking results suggested that all the ligands maintained two hydrogen bond interactions within the active site of HDAC8. Finally, the synthetic accessibility values showed that cinnamon bioactives were easy to synthesize compared to TSA. CONCLUSION : It was evident from both the experimental and computational data that cinnamon bioactives exhibited significant HDAC8 inhibitory activity, thereby suggesting their potential therapeutic implications against cancer.MA Islam was funded by the University of Pretoria Vice Chancellor’s post doctoral and NRF Innovation Post-doctoral fellowship schemes, South Africa, and Choudhari was funded by CSIR Senior Research Fellowship.http://www.phcog.comam2018Chemical Patholog