A Review of the Anti-Cancer Potential of Murraya koenigii (Curry Tree) and Its Active Constituents.

Murraya koenigii (MK) relates to the Rutaceae family and has many health benefits. To date, over eighty-eight carbazole alkaloids along with terpenoids, and other nutrients have been identified from different parts of this plant. This review presents accumulated information regarding the role of MK and its constituents in the prevention/treatment of cancer. Literature survey revealed that MK and its constituents target multiple deranged pathways associated with apoptosis, growth (JAK-STAT, mTOR), and cell cycle in a variety of cancerous cell lines (colon, lung, liver, skin, prostate, breast, etc.) and few animal models. Thus, the present review highlights the anticancer mechanism of MK and its phytoconstituents, and further future perspectives. The ameliorating effects of MK and its phytoconstituents against various cancers warrant its multi-institutional clinical trials as soon as possible. The prospects of relatively cheaper cancer drugs could then be brighter, particularly for the socio-economically feebler cancer patients of the world.

Selenium attenuates venlafaxine hydrochloride-induced testicular damage in mice via modulating oxidative stress and apoptosis.

The present study assessed the effect of selenium (Se) supplementation on Venlafaxine hydrochloride (VH)-induced testicular toxicity. Mice were segregated into Group I (C), Group II (0.5 ppm Se), Group III (VH at a dose 60 mg/kg b.w.) and Group IV (Se was given as per Group II, and VH was given as per Group III). After 10 weeks, sperm parameters, histology, sperm cell counts, antioxidants activities, apoptotic proteins and molecular analysis of testicular tissue were evaluated. Group III had significantly lower sperm concentration (from 2.17 ± 0.28 to 1.04 ± 0.22) and sperm motility (from 68.04 ± 5.5 to 21.47 ± 5.21), and showed an extensive vacuolisation in the germinal epithelium, abnormal basement membrane, and reduced germ cell number as compared to Group I. However, selenium supplementation in Group IV substantially increased sperm concentration (1.47 ± 0.48) and motility (33.27 ± 8.66), improved the histoarchitecture and repopulated the germ cells as observed by raised numbers of spermatogonia, spermatocytes, round spermatids and elongated spermatids contrasted to Group III. Group IV also showed a noteworthy decreased ROS, LPO levels, as well as expressions of Bax, caspase-9, and caspase-3 and increased the SOD, CAT, GPx, and GSH activities as well the expression of Bcl-2 as compared to Group III. This effect was further supported by FTIR analysis for nucleic acids. Thus, selenium supplementation showed significant protection against VH-induced testicular toxicity.

Selenium attenuates bisphenol A incurred damage and apoptosis in mice testes by regulating mitogen-activated protein kinase signalling.

Being a vital micronutrient, along with a trace element, selenium (Se) protects the cells from oxidative stress (OS) in the form of selenoproteins. Bisphenol A (BPA) is a xeno-oestrogenic compound that adversely affects the spermatogenesis process by inducing oxidative stress, which ultimately leads to male infertility. Therefore, it is hypothesised that Se could protect against BPA-induced OS, and further germ cell death by modifying mitogen-activated protein kinase (MAPK) signalling. Male Balb/c mice were divided into four groups: Group I (C) (0.2 ppm Se), Group II (Se) (0.5 ppm Se), Group III (BPA) (0.2 ppm Se, and BPA = 1 mg/kg orally) and Group IV (Se + BPA) (0.5 ppm Se, and BPA = 1 mg/kg bodyweight orally). Results indicated that BPA-treated animals demonstrated a marked decrease in antioxidant enzyme activities (superoxide dismutase, catalase, redox ratio), a marked elevation in the expressions of stress-activated kinases (c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38) and the expressions of pro-apoptotic markers (caspase-9, caspase-8 and caspase-3). However, Se supplementation considerably restored the antioxidant enzyme activities and lowered the expressions of stress-activated kinases, which further down-regulated the apoptosis. Thus, Se supplementation demonstrated to be effective against BPA provoked testicular damage.

Chemopreventive activity of hydroethanolic Murraya koenigii leaves extract (HEMKLE) against chemically induced skin carcinogenesis in mice.

The present study aimed to examine the chemoprotective effect of Hydroethanolic Murraya koenigii leaves extract (HEMKLE) on murine skin carcinogenesis model. For the study, male LACA mice divided into four groups (n = 15 per group). Group I (Control), Group II (DMBA/TPA), Group III (HEMKLE), and Group IV (HEMKLE + DMBA/TPA). Skin tumors were induced in Group II (DMBA/TPA) and Group IV (HEMKLE + DMBA/TPA) by topical application of 7, 12 dimethylbenz[a]anthracene (DMBA) [500 nmol/100 µL of acetone, twice a week for two weeks] and 12-O-tetradecanoyl phorbol-13-acetate (TPA) [1.7 nmol/100 µL of acetone, twice a week for eighteen weeks] and HEMKLE (200 mg/kg b. w.) was administered orally (instilled by oral gavage). The chemoprotective response of HEMKLE was evident by inhibition in tumor incidence, mean tumor volume, mean tumor burden, total number of tumors, and tumor size in Group IV (HEMKLE + DMBA/TPA) when compared to Group II (DMBA/TPA). HEMKLE administration also decreased the reactive oxygen species (ROS) and lipid peroxidation (LPO) levels and increased the antioxidants enzyme activities in Group IV (HEMKLE + DMBA/TPA) when compared to Group II (DMBA/TPA) that suggests its antioxidant potential. HEMKLE administration also increased the mRNA and protein expression of caspase-9 and caspase-3 and decreased the mRNA and protein expression of Bcl-2 in Group IV (HEMKLE + DMBA/TPA) when compared to Group II (DMBA/TPA) that suggest its apoptosis-inducing effect on DMBA/TPA induced skin carcinogenesis.

Studies on the ameliorative potential of dietary supplemented selenium on doxorubicin-induced testicular damage in mice.

Doxorubicin, a chemotherapeutic drug, is known to disrupt the normal spermatogenesis by excess oxidative stress. The present study describes the curative effects of dietary supplemented selenium on doxorubicin-induced testicular damage in mice. Four groups were included in the study: Group I(C), Group II (Se-0.5 ppm/kg diet), Group III (Dox-3mg/kg body weight i.p.) and Group IV (Se + Dox). We analysed microscopic sperm parameters, histopathology, testicular germ cell kinetics, oxidative stress levels, antioxidant levels and mRNA expression studies of apoptotic and stress response markers. Sperm parameters were significantly reduced in doxorubicin-treated group. Moreover, mice treated with doxorubicin showed an elevation in oxidative stress markers as well as decreased redox ratio, and antioxidant levels were observed in Group III (Dox). However, selenium supplementation ameliorated the damage incurred by doxorubicin, by improving sperm parameters, antioxidant levels and histoarchitecture of mice testes, and decreased the oxidative stress levels. Selenium administration also reduced the levels of apoptotic caspases and stress-activated kinases in Group IV (Se + Dox) when compared to Group III (Dox). In conclusion, selenium exhibits the curative effect against doxorubicin-induced testicular damage in mice by attenuating stress conditions and associated apoptosis.

Alleviating impact of hydroethanolic Murraya koenigii leaves extract on bisphenol A instigated testicular lethality and apoptosis in mice.

Bisphenol A (BPA) is a well-known endocrine disruptor that imposees adverse effects on male fertility via interacting with germ cells of testis. Objectives of present study were to investigate the possible protective effects of hydroethanolic Murraya koenigii leaves extract (HEMKLE) against BPA-induced testicular damage and apoptosis in mice. Male Balb/c mice were divided into four different groups: Group I (control), Group II (HEMKLE), Group III (BPA) and Group IV (HEMKLE + BPA). Group III (BPA) showed significant decrease in sperm parameters, germ cell number along with increased lipid peroxidation (LPO) and reactive oxygen species (ROS). A significant decrease in antioxidant enzymes activity was also observed in Group III (BPA) animals. mRNA expression study revealed significant decrease in the expression of Bcl-2 and increase in expressions of caspase-9 and caspase-3, thus clearly demonstrate BPA-induced apoptosis. In addition, HEMKLE co-administration to BPA-treated mice showed a significant increase in sperm parameters, germ cell number, decreased levels of LPO and ROS, increased antioxidant enzymes activity in Group IV (HEMKLE + BPA). Also, mRNA expression study showed a significant increase in Bcl-2 and decrease in caspase-9 and caspase-3 gene expressions in Group IV (HEMKLE + BPA). Thus, the present study suggests that HEMKLE intervention provides protection against BPA-induced oxidative stress and apoptosis.

Lycopene enriched tomato extract suppresses chemically induced skin tumorigenesis in mice.

The present study revealed the effects of Lycopene enriched tomato extract (LycT) on chemically induced skin cancer in mice. Skin tumors were induced by topical application of 7,12-Dimethylbenz(a)anthracene (DMBA) [500 nmol/100 ul of acetone, twice a week for two weeks] and 12-O-tetradecanoyl phorbol-13-acetate (TPA) [1.7 nmol/100 ul of acetone, twice a week for eighteen weeks] and LycT (5 mg/kg b.w.) was administered orally. Male Balb/c mice were divided into four groups (n = 15 per group): control, DMBA/TPA, LycT and LycT + DMBA/TPA. The chemopreventive response of LycT to skin tumorigenesis was evident by inhibition in tumor incidence, number, size, burden and volume in LycT + DMBA/TPA group when compared to DMBA/TPA group. This was associated with inhibition of cell proliferation in LycT + DMBA/TPA group as observed by the decrease in epidermal morphometric parameters and mRNA and protein expression of proliferating cell nuclear antigen when compared to DMBA/TPA group (p ≤ 0.05). LycT decreased (p ≤ 0.05) the mRNA and protein expression of angiogenic genes (vascular endothelial growth factor, angiopoietin-2, basic fibroblast growth factor) in LycT + DMBA/TPA group, suggesting its anti-angiogenic effects. The increase (p ≤ 0.05) in protein expression of connexin-32 and 43 in LycT + DMBA/TPA group suggests improved inter cellular communication when compared to DMBA/TPA group. Histochemical studies demonstrated that the components of extracellular matrix (fibrous proteins and mucopolysaccharides) were also modulated during skin carcinogenesis and its chemoprevention by LycT. The decrease in cell proliferation parameters and expression of angiogenesis associated genes, modulation of ECM components and increase in expression of connexins suggest that LycT improved multiple dysregulated processes during chemoprevention of skin cancer.