Tobacco chewing and smoking are major risk factors for oral cancer, with Oral Squamous Cell Carcinoma (OSCC), comprising approximately 90

OBJECTIVE:Triple-Negative Breast Cancer (TNBC), the most challenging subtype of Breast Cancer (BC), currently lacks targeted therapy, presenting a significant therapeutic gap in its management. Tumor Associated Macrophages (TAMs) play a significant role in TNBC progression and could be targeted by repolarizing them from M2 to M1 phenotype. Matairesinol (MAT), a plant lignan, has been shown to exhibit anticancer, anti-inflammatory and immunomodulatory activities. In this study, we explored how MAT-induced repolarization of THP-1-derived M2 macrophages towards the M1 phenotype, which could effectively target the TNBC cell line, MDA-MB-231. METHODS:The differential expression of genes in THP-1-derived macrophages at mRNA levels was evaluated by RNAseq assay. An inverted microscope equipped with a CMOS camera was utilized to capture the morphological variations in THP-1 cells and THP-1-derived macrophages. Relative mRNA expression of M1 and M2 specific marker genes was quantified by qRT-PCR. Cell viability and induction of apoptosis were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1 dye) assays, respectively. RESULTS:MAT reduced the viability of M2a and M2d macrophages and repolarized them to M1 phenotype. Conditioned medium (CM) from MAT-treated M2a and M2d macrophages significantly reduced the viability of TNBC cells by apoptosis. CONCLUSION:Targeting M2 macrophages is an important strategy to regulate cancer progression. Our study provides evidence that MAT may be a promising drug candidate for developing novel anti-TNBC therapy. However, further studies are warranted to thoroughly elucidate the molecular mechanism of action of MAT and evaluate its therapeutic potential in TNBC in vitro and in vivo models.

Cervical cancer, the fourth most common cancer globally and the second most prevalent cancer among women in India, is primarily caused by Human Papilloma Virus (HPV). The association of diet with cancer etiology and prevention has been well established and nutrition has been shown to regulate cancer through modulation of epigenetic markers. Dietary fatty acids, especially omega-3, reduce the risk of cancer by preventing or reversing the progression through a variety of cellular targets, including epigenetic regulation. In this work, we have evaluated the potential of ALA (α linolenic acid), an ω-3 fatty acid, to regulate cervical cancer through epigenetic mechanisms. The effect of ALA was evaluated on the regulation of histone deacetylases1, DNA methyltransferases 1, and 3b, and global DNA methylation by ELISA. RT-PCR was utilized to assess the expression of tumor regulatory genes (hTERT, DAPK, RARβ, and CDH1) and their promoter methylation in HeLa (HPV18-positive), SiHa (HPV16-positive) and C33a (HPV-negative) cervical cancer cell lines. ALA increased DNA demethylase, HMTs, and HATs while decreasing global DNA methylation, DNMT, HDMs, and HDACs mRNA expression/activity in all cervical cancer cell lines. ALA downregulated hTERT oncogene while upregulating the mRNA expression of TSGs (Tumor Suppressor Genes) CDH1, RARβ, and DAPK in all the cell lines. ALA reduced methylation in the 5’ CpG island of CDH1, RARβ, and DAPK1 promoters and reduced global DNA methylation in cervical cancer cell lines. These results suggest that ALA regulates the growth of cervical cancer cells by targeting epigenetic markers, shedding light on its potential therapeutic role in cervical cancer management.

Background In India, cancer of the cervix is the second most common cancer in women. Nowadays, various traditional herbal formulations can be used as adjuncts during conventional cancer therapies due to their anticancer activity. Habbe Musaffi Khoon (HMK), a Unani compound formulation, is traditionally used as a blood purifier and thus used to treat boils, scabies, acne, and pimples. It is also indicated in skin diseases, Habis-ud-Dam (styptic), and therapeutically used in Nafz-ud-Dam (hemorrhagic).Objectives The main purpose of this work was to phytochemically characterize HMK aqueous extract (HMKaq) and determine its activity against cervical cancer cells.Materials and Methods HMKaq was subjected to liquid chromatography-mass spectrometry (LC-MS) and evaluated for the presence of phytocompounds. HMKaq was evaluated for its effect on the viability of cervical cancer cells (HeLa, SiHa, and C33A) and was determined by MTT assay. Trypan blue dye exclusion was used to determine the outcome of HMKaq on the growth kinetics of cervical cancer cells. The role of HMK in regulating the cell cycle was analyzed by FACS and its effect on apoptosis was evaluated by checking mitochondrial membrane potential readings of JC-1 aggregates on a microplate reader and on the mRNA expression of caspase-3 and cytochrome c was evaluated by PCR.Results LC-MS analysis revealed 3845 compounds, out of which 58 were the major compounds. These included phenolics, esters, fatty acids, furans, quinones, tannins, flavonoids, and terpenes. HMKaq reduced the viability and growth of the cells. It induced arrest in the cell cycle of HeLa and apoptosis in SiHa and C33A by depolarizing the membrane potential of the mitochondria and upregulation of mRNA expression of Cas3 and Cyt C.Conclusion HMK exhibited anticancer activity against cervical cancer cells, thereby signifying its therapeutic potential.

Background In India, cancer of the cervix is the second most common cancer in women. Nowadays, various traditional herbal formulations can be used as adjuncts during conventional cancer therapies due to their anticancer activity. Habbe Musaffi Khoon (HMK), a Unani compound formulation, is traditionally used as a blood purifier and thus used to treat boils, scabies, acne, and pimples. It is also indicated in skin diseases, Habis-ud-Dam (styptic), and therapeutically used in Nafz-ud-Dam (hemorrhagic). Objectives The main purpose of this work was to phytochemically characterize HMK aqueous extract (HMKaq) and determine its activity against cervical cancer cells. Materials and Methods HMKaq was subjected to liquid chromatography-mass spectrometry (LC-MS) and evaluated for the presence of phytocompounds. HMKaq was evaluated for its effect on the viability of cervical cancer cells (HeLa, SiHa, and C33A) and was determined by MTT assay. Trypan blue dye exclusion was used to determine the outcome of HMKaq on the growth kinetics of cervical cancer cells. The role of HMK in regulating the cell cycle was analyzed by FACS and its effect on apoptosis was evaluated by checking mitochondrial membrane potential readings of JC-1 aggregates on a microplate reader and on the mRNA expression of caspase-3 and cytochrome C was evaluated by PCR. Results LC-MS analysis revealed 3845 compounds, out of which 58 were the major compounds. These included phenolics, esters, fatty acids, furans, quinones, tannins, flavonoids, and terpenes. HMKaq reduced the viability and growth of the cells. It induced arrest in the cell cycle of HeLa and apoptosis in SiHa and C33A by depolarizing the membrane potential of the mitochondria and upregulation of mRNA expression of Cas3 and Cyt C. Conclusion HMK exhibited anticancer activity against cervical cancer cells, thereby signifying its therapeutic potential. Keywords Cancer/oncology , Complementary and Alternative Medicine (CAM) , other cancer therapies , women and health

Ethnopharmacological relevance: Panchvalkala, an Ayurvedic traditional formulation has references in Charak Samhita and Bhavaprakasha Nighantu for the treatment of women with endometriosis-related problems, leucorrhea and vaginal ailments. The formulation comprises of equal ratios of the barks from Ficus glomerata, Ficus virens, Ficus religiosa, Ficus benghalensis, and Thespesia populnea. Aim of the study: The present study aimed to evaluate the anticancer and immunomodulatory activity of aqueous extract of Panchvalkala (PVaq) against cervical cancer in vitro and in vivo. Materials and methods: The effect of PVaq on disruption of mitochondrial membrane potential in cervical cancer cell lines, SiHa and HeLa, was studied by using JC1 dye. The expression of generic caspases in the cells after treatment with PVaq was evaluated by ELISA kit. The expression of pRb, p53, E6 and E7 proteins were evaluated by western blotting. Acute oral toxicity and DRF studies were performed in Swiss albino mice by following OECD guidelines 423 and 407, respectively. Tumor retardation study was done in C57BL/6 mouse papilloma model. The mice were divided into six groups: No tumor control (NTC), Tumor control (TC), Cisplatin (Cis) (4 mg/kg b. w.), PVaq 100, 200 mg/kg b.w and combination of PVaq (200 mg/kg b.w.) and Cisplatin (4 mg/kg b.w.). The mice were orally gavaged with PVaq daily for 14 days and cisplatin was given intravenously on every 1st, 5th and 9th day. Hematological and biochemical parameters were studied by using hematology analyzer and kits, respectively. E6 and E7 gene expression in the tumor samples was determined by qPCR. Th1 and Th2 cytokine levels were determined by ELISA. Results: PVaq induced mitochondrial depolarization in SiHa and HeLa, and increased the expression of generic caspases, resulting into apoptosis. PVaq upregulated the expression of tumor suppressor proteins (p53 and pRb) and reduced the expression of viral oncoproteins (E6 and E7). Acute toxicity study displayed non-toxicity of PVaq while DRF study ensured its safe dose for further efficacy studies. PVaq reduced tumor volume and weight in mouse papilloma model and induced immunomodulation in the animals. It increased serum levels of IL-2 (Th1) with a concomitant decrease in IL-10 (Th2) cytokines. The drug did not affect body weight, food consumption and organ histopathology of the animals. Conclusions: PVaq exhibited anticancer and immunomodulatory activities against cervical cancer cells and female mouse papilloma model.

Background: HC9, a polyherbal formulation, is based on Stanyashodhana Kashaya (an Ayurvedic formulation) that is being prescribed by Ayurvedic physicians for the treatment of various disorders of mammary glands. We have recently reported anticancer activity of HC9 in breast cancer cell lines through various molecular mechanisms. Few studies have shown an association between breast cancer and melanoma that has prompted us to find whether HC9 could regulate the melanoma growth as well. Aim of the Study: The aim was to investigate the tumor retardation and immunomodulatory potential of HC9 in mouse melanoma model. Materials and Methods: C57BL/ 6 mice, with B16F10-induced melanoma tumors, were divided into six groups: tumor control, doxorubicin (2 mg/kg body weight [b. w.]), low dose (100 mg/kg b.w.), intermediate (200 mg/kg b.w.), and high dose (400 mg/kg b.w.) of HC9. No tumor control served as the negative control group. The mice were orally gavaged with HC9 daily for 3 weeks. The urine and blood samples from all the animals were taken before necropsy. The expression of T-helper type 1 (Th1) (interferon-. and interleukin [IL]-2) and Th2 (IL-4 and IL-10) serum cytokines was evaluated by ELISA assay. Results: HC9 significantly retarded the tumor growth in C57BL/6 mouse melanoma model. The animals did not show any changes in body weight and food consumption throughout the study period. Urine and histopathological analysis revealed no signs of toxicity in HC9-treated animals. HC9 appreciably increased the serum levels of Th1 with a concomitant decrease in Th2 cytokines. Conclusion: HC9 retarded the tumor growth in mouse melanoma model and induced immunomodulation, thereby suggesting the potential of the formulation against melanomas.

Cervical cancer is the second leading cause of cancer death in women in India. Previously, we have reported that alpha linolenic acid (ALA), induced apoptosis in cervical cancer cell lines and reduced expression of E6 and E7 oncoproteins with simultaneous decrease in Cox2/VEGF/MAP kinase proteins. Here, we investigated the tumor retardation potential of flax oil (FO), rich in ALA, in mouse papilloma model. Flax oil significantly reduced tumor volume and weight in mice compared to the Tumor control (TC) group. Interestingly, compared to cisplatin (Cis) alone, there was slightly enhanced decrease in tumor weight when FO was given together with Cis (Cis + FO). A marked increase in plasma antioxidant levels in mice, and increase in lipid peroxidation in tumors with simultaneous decrease in liver tissues was observed in Cis + FO group compared to either TC or Cis groups. FO and Cis + FO significantly modulated immune response in mice by increasing CD8 alpha and IFN gamma and decreasing IL-4 expression. Interestingly, when given together with cisplatin, flax oil reduced HPV E6 and E7 oncoprotein expression with concomitant increase in the relative mRNA expression of tumor suppressor genes p53 and Rb. Thus, flax oil could be explored for its therapeutic potential in cervical cancer.

Ethnopharmacological relevance: HC9, a polyherbal formulation, is based upon a traditional Ayurvedic formulation, Stanya Shodhana Kashaya (SSK, having 10 plant materials), formulated on Stanyashodhana gana, explained by Charaka in Charakasalphita Sutrasthana IV and mentioned in other texts as well. Stanyasodhana is the Sanskrit name for a group of medicinal plants, classified for "improving the quality of milk". SSK is used by Ayurvedic practitioners for the cleansing and detoxification of breast milk in lactating mothers as well as for the management of various clinical conditions. HC9 is composed of equal ratios of nine different medicinal plants that include Picrorhiza kurroa Royle ex Benth., Cyperus rotundus L., Zingiber officinale Roscoe, Cedrus deodara (Roxb. ex D.Don) G.Don, Tinospora cordifolia (Willd.) Miers, Holarrhena antidysenterica (Roth) Wall. ex A.DC., Swertia chirata Buch.-Ham. ex Wall., Cissampelos pareira L. and Hemidesmus indicus (L.) R. Br. ex Schult.. It differs from the SSK formulation by having one ingredient [Marsdenia tenacissima (Roxb.)Moon (Murva)] less, due to its unavailability since it is mostly found in tropical hilly tracts of peninsular India and Vindhya ranges as well as in lower Himalayan tracts. All the medicinal plants in the formulation have reported activity against different types of cancers. Aim of the study: The present study is aimed at evaluating the anticancer activity of the polyherbal formulation (HC9) and its mechanism of action against breast cancer cell lines. Materials and Methods: The effect of HC9 on the viability of breast cancer (MCF-7 and MDAMB231) and non-cancerous (MCF-10A) cell lines was evaluated by MTT assay. The effect on cell growth and colony formation potential of cancer cells was determined by trypan blue dye exclusion method and soft agar assay, respectively. Cell cycle arrest was determined by propidium iodide (PI) staining and analyzed by flowcytometer. Scratch wound assay was used for studying cell migration. Cell invasion was determined by using BD BioCoat Matrigel invasion chambers. The gene expression of HIF-1 alpha was examined by RT-PCR. The expression of p53, SMAR1, pI6, MMP-2, CDP/Cux, p21, Rb, phospo-Rb (ppRb), VEGF, NFKB and COX-2 proteins was determined by western blotting. Results: HC9 significantly altered growth of breast cancer cell lines, MCF-7 and MDA MB-231. It blocked the cell cycle progression at S phase in MCF-7 by up regulating the expression of p53, p21 and p16 proteins. In MDA MB-231, HC9 induced G1 phase arrest by up regulating the expression of p53, p21 and pRb proteins with simultaneous decrease in ppRb. It significantly reduced migration and invasion in both the cell lines, accompanied by decrease in the expression of MMP-2/9, HIF-1 alpha and VEGF. HC9 decreased the expression of inflammatory markers (NF-KB, COX-2), and modulated the expression of chromatin modulators (SMAR1 and CDP/Cux) in both MCF-7 and MDA MB-231. Conclusions: HC9 exhibited potent anticancer activity against breast cancer cells, thereby warranting further pre-clinical and clinical studies in future.

A 38-year-old female patient was diagnosed with third episode of breast abscess that was evacuated and drained by cupping therapy, followed by application of raw papaya dressing. Unani medicines were prescribed during the course of the treatment for fifty days. It was observed that the wound healed up with no episode of recurrence of breast abscess. The breast abscess was successfully treated with Unani therapeutic approach.

Background: Ocimum sanctum (OSE) has been used in the Indian system of traditional medicine (Ayurveda) for the treatment and prevention of various diseases. However, the contradictory reports regarding the reproductive safety of OSE prompted us to re-verify its effect on the reproductive system by following internationally accepted Organization for Economic Cooperation and Development guideline 415. Objective: To study the effect of aqueous/methanolic extract of OSE (OciBest) on the male and female reproductive performance of Wistar rats. Materials and Methods: Rats were orally gavaged with OciBest at dose levels of 0, 250, 500, and 1000 mg/kg. Males were administered with OciBest for 12 weeks before and during the mating period. On the other hand, females received OciBest for 2 weeks before mating until the end of the lactation period. Results: OciBest at 1000 mg/kg did not induce any adverse effects on the reproductive performance of male and female rats. All the treated parent animals survived until the end of the study period with no major signs of clinical toxicity. The body weights, food consumption, male and female fertility indices, organ weights, as well as gross pathological and histopathology observations in parent animals, did not reveal any treatment-related adverse effects. Moreover, in comparison to the control groups, OciBest did not induce any treatment-related adverse effects to the offsprings. Conclusion: Thus, no-observed adverse effect level was found up to 1000 mg/kg dose, suggesting the safety of OciBest for reproductive system.

BACKGROUND:Triphala, an Ayurvedic polyherbal formulation, is used for the treatment of various diseases including obesity.OBJECTIVE:The present study was planned to evaluate the anti-adipogenic potential of aqueous extract of Triphala (TPaq) using 3T3-L1 adipocyte cell line model.METHODS:The effect of aqueous extract of Triphala (TPaq) was tested on the viability of 3T3- L1 cells by MTT assay. The cells were treated with a cocktail of dexamethasone (DEX), isobutylmethylxanthine (IBMX) and insulin to induce adipogenesis. The cells were treated either with the induction cocktail or with the cocktail containing different concentrations (1, 10 and100 μg/ml) of TPaq. Intracellular lipid content was analyzed using Oil O Red stain and was quantified after extracting with isopropanol at 500 nm wavelength. The expression of early (PPAR-γ and C/EBP-α) and late (GLUT4 and FAS) phase adipogenic genes was studied by real time PCR.RESULTS:TPaq did not affect the viability of 3T3-L1 cell line. Interestingly, TPaq induced a concentration dependant decrease in the intracellular lipid content and expression of both early and late phase adipogenic genes. This decrease was statistically significant compared to cells treated with only induction cocktail.CONCLUSION:These results suggested that Triphala regulated lipid accumulation by down regulating expression of adipogenic genes, resulting into prevention of adipogenesis.SUMMARY:The purpose of this study was to evaluate the effect of an ayurvedic polyherbal drug Triphala on adipogenesis using 3T3-L1 cell line. The results suggested that Triphala regulated lipid accumulation by downregulating expression of adipogenic genes, resulting into the prevention of adipogenesis. Abbreviations used: TPaq: Aqueous extract of Triphala; DMEM: Dulbecco's Modified Eagle's medium; FBS: Fetal Bovine Serum; IBMX: Isobutyl methylxanthine; DMX: Dexamethasone; MTT: [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay; PPARγ: Peroxisome proliferator-activated receptor; C/EBP:Enhancer binding protein α, FAS:Fatty acid synthase; Glut-4: Glucose phosphate transporter 4.

Background: Cervical cancer is the most common malignant disease affecting women worldwide. The currently available therapies for cancer, even though effective, affect the patient's health severely due to the associated side effects. Thus, nowadays, complementary/alternative medicines are being extensively researched upon for their use as an adjunct therapy. Panchavalkala, an Ayurvedic formulation, is traditionally being used as a douche in leukorrhea and other gynecological diseases. Objective: The objective of the study was to phytochemically standardize aqueous extract of Panchavalkala (PVaq) and evaluate its anticancer activity against human cervical cancer cell lines. Materials and Methods: The phytochemical characterization of PVaq was done by liquid chromatography-mass spectrometry (LCMS) technique. The effect of PVaq on the viability of SiHa and HeLa cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide dye assay. The effect of the extract on growth kinetics was evaluated by trypan blue dye exclusion method and soft agar assay. Results: LCMS analysis showed presence of 77 compounds, of which 15 major compounds included proanthocyanidin B1, chlorogenic acid, caffeic acid, epicatechin, leucopelargonidin 3-O-alpha-L-rhamno-beta-D-glucopyranoside, leucocyanidin, naringenin-7-o-glucoside, mesoinositol, catechin, vogelin E, mesoinositol, behenic acid, bergenin, acacetin, and gallic acid. PVaq significantly (P < 0.001) reduced the viability of SiHa and HeLa cells with an IC50 of 125.8 and 96.0 mu g/ml, respectively. It also reduced the growth of cervical cancer cells in a dose- and time-dependent manner. Conclusion: This preliminary data suggests that PVaq exhibits potential anticancer activity and warrants further studies for detailed elucidation of its mechanism of action.

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 potential 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. SUMMARY:Pharmacoinformatics studies revealed that cinnamon bioactives bound to the active site of HDAC8 enzyme in a way similar to that of TSAThe molecular descriptors of cinnamon compounds successfully correlated with TSA values. The binding interactions and energies were also found to be close to TSASynthetic accessibility values showed that cinnamon bioactives were easy to synthesize compared to TSA. Abbreviations used: ACE: Aqueous Cinnamon Extract; DFT: Density Function Theory; CAL: Cinnamaldehyde; CA: Cinnamic Acid; CALC: Cinnamyl Alcohol; MW: Molecular Weight; ROTBs: Rotatable Bonds; ROF: Lipinski's Rule of Five; TSA: Trichostatin A; PDB: Protein Data Bank; RMSD: Root Mean Square Deviation; HBA: Hydrogen Bond Acceptor; HBD: Hydrogen Bond Donor; ADMET: Absorption, Distribution, Metabolism, Excretion and Toxicity; FO: Frontier Orbital; HOMOs: Highest Occupied Molecular Orbitals; LUMOs: Lowest Unoccupied Molecular Orbitals; BE: Binding Energy.

Aim: The present study evaluated the effect of ethanolic extract of Nardostachys jatamansi roots (NJ(et)) on MYCN mediated regulation of expression of MDM2 and p53 proteins in neuroblastoma cell lines, IMR-32 and SK-N-MC. Materials and Methods: The effect of NJ(et) on cell viability was determined by MTT and on growth kinetics was evaluated by trypan blue dye exclusion method and soft agar assay. The expression of p53, MDM2 and MYCN proteins in response to NJe, treatment was evaluated by immunoblotting. Results: NJ(et) decreased the viability of neuroblastoma cells without affecting the viability of non-cancerous, HEK-293 cells. It altered the growth kinetics of the cancer cells in a dose-dependent manner. NJ,, down regulated the expression of MYCN and MDM2 proteins with a simultaneous increase in the expression of tumor suppressor protein p53. Conclusions: The present data demonstrated that NJe regulated the growth of IMR-32 and SK-N-MC through reduction in MYCN expression that lead to down regulation of MDM2 protein and increase in p53 expression. These preliminary results warrant further in depth studies to explore the therapeutic potential of Nardostachys jatamansi in the management of neuroblastoma.

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 cancer

The present study has compared the anti-inflammatory activity of aqueous (OBW) and methanolic (OBM) extracts of aerial parts of Ocimum basilicum in macrophage (RAW264.7) and human chondrosarcoma (SW1353) cell lines, and human primary chondrocytes to correlate their efficacy in terms of management of osteoarthritis (OA). In RAW264.7, OBW decreased nitric oxide (NO) (35% +/- 0.22) and prostaglandin (PGE(2)) (70.8% +/- 0.93) production more effectively compared with OBM. Interestingly, decrease in NO was accompanied by a corresponding decrease in inducible nitric oxide synthase (iNOS) (71.4 +/- 2.43%) protein expression. OBW decreased total nuclear factor-kappa B (NF kappa B) (79.28% +/- 1.8) and cyclooxygenase (COX)-2 (83.87% +/- 0.95) proteins significantly (p < 0.001), compared with OBM. Similarly, in SW1353 and chondrocytes, OBW decreased PGE(2) (76.11% +/- 5.5) and leukotriene (LTB4) (59.6% +/- 0.22) production appreciably (p < 0.001), compared with OBM. In chondrocytes, OBW reduced the production of matrix metalloproteinase (MMP)-2 (58.49% +/- 1.41), -9 (43.13% +/- 2.82) and -13 (54.54% +/- 2.12) significantly more (p < 0.001), than OBM, All these data suggest that compared with the methanolic extract, the aqueous extract of O. basilicum could be explored for its potential applications in the management of inflammatory conditions associated with OA. (C) 2016 Elsevier GmbH. All rights reserved.

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 (CC W ) and C. zeylanicum (CZ W ) and methanolic extracts of C. cassia (CC M ) and C. zeylanicum (CZ M ) at various concentrations (0.1-100 µg/ml) for 1 h, followed by stimulation with LPS and IL-1β, respectively. The effect of CC M , CC W , CZ M and CZ W on the production of nitric oxide (NO) was evaluated by Griess reaction. Evaluation of prostaglandin E 2 (PGE 2 ) and leukotriene (LTB 4 ) 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 (CC M , CZ M ) of both the varieties of cinnamon were found to be more effective than the aqueous extracts in terms of PGE 2 , LTB4 and MMP inhibition. We found that in RAW 264.7, CC M and CZ M decreased NO and PGE 2 production by45.40%±8.6; 65.63%±5.7 and 79.88%±1.2; 95.91%±0.3, respectively. Similarly, in SW1353 and chondrocytes, CC M decreased PGE 2 production by 68.8%±6.4;36.1%±9.5, respectively whereas CZ M reduced PGE 2 production by 70.2%±2.3; 52.3%±5.4, respectively. Moreover, in SW1353 and chondrocytes CC M decreased LTB4 production by 85.47%±3.03; 99.6%±0.2, respectively whereas CZ M reduced LTB4 production by 67.5%±5.6; 75.6%±1.2, respectively. In chondrocytes both CC M and CZ M 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. zeylanicum was 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.

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 (𝑛=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 an 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.

Ethnopharmacological relevance: Ocimum sanctum, commonly known as Holy Basil or Tulsi has been used in Ayurveda as a demulcent, stimulant, expectorant; in the treatment of bronchitis, skin infections, malaria, diarrhoea, dysentery, arthritis, gastric and inflammatory disorders. We have previously shown that methanolic/aqueous extract of O. sanctum did not induce genotoxicity and other toxic effects in acute oral toxicity study. In the present report, we have performed sub-acute toxicity of methanolic/aqueous preparation of O. sanctum in Wistar rats to evaluate whether it induced any chronic toxic effects.Materials and methods: In subacute toxicity study, animals received 0. sanctum extract (OSE) by oral gavage at the doses of 250, 500 and 1000 mg/kg/day (n=5/group/sex) for 28 days. At the end of the study, the animals were sacrificed and evaluated for the effect of OSE on clinical, haematological, biochemical and histopathological parameters.Results: The rats treated with OSE did not show any change in body weight, food and water consumption, motor activity, sensory reactivity and foot splay measurements. There were no significant changes in haematological, pathological and biochemical parameters; and histopathology of tissues (liver, kidney, spleen, heart, and testis/ovary) among rats of either sex. OSE at a dose of 1000 mg/kg showed significant increase of Mean corpuscular hemoglobin (MCH) (19.8 +/- 0.8; 18.7 +/- 0.5) and mean corpuscular hemoglobin concentration (MCHC) (41.8 +/- 1.1; 39.3 +/- 0.7) in male and female rats in comparison to their respective controls (MCH: 17.7 +/- 0.3; 17.4 +/- 0.3; MCHC: 37.8 +/- 0.5; 36.1 +/- 0.2). Urine parameters (appearance, blood, nitrate, leucocyte, glucose, ketone, pH, protein and specific gravity) in both the male and female rats were comparable to their respective controls. In addition, no changes were observed in the vital organs of rats at macroscopic and microscopic levels.Conclusions: Our results showed that oral administration of OSE was not toxic to male and female Wistar rats upto the highest dose tested, thereby suggesting its clinical usefulness. (C) 2015 Elsevier Ireland Ltd. All rights reserved.