Although Piper sarmentosum (PS) is known to possess the antidiabetic properties, its efficacy towards diabetic cardiovascular tissues is still obscured. The present study aimed to observe the electron microscopic changes on the cardiac tissue and proximal aorta of experimental rats treated with PS extract. Thirty-two male Sprague-Dawley rats were divided into four groups: untreated control group (C), PS-treated control group (CTx), untreated diabetic group (D), and PS-treated diabetic group (DTx). Intramuscular injection of streptozotocin (STZ, 50 mg/kg body weight) was given to induce diabetes. Following 28 days of diabetes induction, PS extract (0.125 g/kg body weight) was administered orally for 28 days. Body weight, fasting blood glucose, and urine glucose levels were measured at 4-week interval. At the end of the study, cardiac tissues and the aorta were viewed under transmission electron microscope (TEM). DTx group showed increase in body weight and decrease in fasting blood glucose and urine glucose level compared to the D group. Under TEM study, DTx group showed lesser ultrastructural degenerative changes in the cardiac tissues and the proximal aorta compared to the D group. The results indicate that PS restores ultrastructural integrity in the diabetic cardiovascular tissues.
Gynura bicolor (Compositae) which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water) of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116), one human breast adenocarcinoma cell line (MCF7), and one human normal colon cell line (CCD-18Co) were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay), possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor.
In continuation of our interest towards the elucidation of apoptotic pathways of cytotoxic phytocompounds, we have embarked upon a study on the anticancer effects of 7α-hydroxy-β-sitosterol (CT1), a rare natural phytosterol oxide isolated from Chisocheton tomentosus. CT1 was found to be cytotoxic on three different human tumor cell lines with minimal effects on normal cell controls, where cell viability levels were maintained ≥80% upon treatment. Our results showed that cell death in MCF-7 breast tumor cells was achieved through the induction of apoptosis via downregulation of the ERK1/2 signaling pathway. CT1 was also found to increase proapoptotic Bax protein levels, while decreasing anti-apoptotic Bcl-2 protein levels, suggesting the involvement of the intrinsic pathway. Reduced levels of initiator procaspase-9 and executioner procaspase-3 were also observed following CT1 exposure, confirming the involvement of cytochrome c-mediated apoptosis via the mitochondrial pathway. These results demonstrated the cytotoxic and apoptotic ability of 7α-hydroxy-β-sitosterol and suggest its potential anti-cancer use particularly on breast adenocarcinoma cells.
Phyllanthus is a traditional medicinal plant that has been found to have antihepatitis, antibacterial, and anticancer properties. The present studies were to investigate the in vitro molecular mechanisms of anticancer effects of Phyllanthus (P. amarus, P. niruri, P. urinaria, and P. watsonii) plant extracts in human prostate adenocarcinoma. The cancer ten-pathway reporter array was performed and revealed that the expression of six pathway reporters were significantly decreased (Wnt, NFκB, Myc/Max, hypoxia, MAPK/ERK, and MAPK/JNK) in PC-3 cells after treatment with Phyllanthus extracts. Western blot was conducted and identified several signalling molecules that were affected in the signalling pathways including pan-Ras, c-Raf, RSK, Elk1, c-Jun, JNK1/2, p38 MAPK, c-myc, DSH, β-catenin, Akt, HIF-1α, GSK3β, NFκB p50 and p52, Bcl-2, Bax, and VEGF, in treated PC-3 cells. A proteomics-based approach, 2D gel electrophoresis, was performed, and mass spectrometry (MS/MS) results revealed that there were 72 differentially expressed proteins identified in treated PC-3 cells and were involved in tumour cell adhesion, apoptosis, glycogenesis and glycolysis, metastasis, angiogenesis, and protein synthesis and energy metabolism. Overall, these findings suggest that Phyllanthus can interfere with multiple signalling cascades involved in tumorigenesis and be used as a potential therapeutic candidate for treatment of cancer.
Edible bird's nest (EBN) which is solidified swiftlet's saliva contains high nutritional value. It is widely consumed in countries like Malaysia, Indonesia, and Thailand. However, previous proximate analysis of Malaysia EBN was not representative of all the regions in Malaysia. In recent years, safety issues such as high nitrate and nitrite contents, presence of heavy metal, adulteration, fungal infection, and cancer cell stimulation were associated with EBN. Hence, this study aimed to determine the proximate analysis, safety profile during normal weather and hazy periods, and its effect on cancer cells stimulation in Malaysia-farmed EBN. Seven raw cleaned EBN samples were sourced from 6 different regions in Malaysia. Proximate analysis and safety profile were performed using official AOCA methods and Malaysian Standard. High protein (53.03-56.37%) and carbohydrate content (27.97-31.68%) with an acceptable level of moisture (10.8-14.04%) and ash (2.22-3.38%) were reported. A good safety profile was obtained with low nitrite and nitrate levels, with undetectable heavy metals and no significant growth of pathogenic microorganism except mould. Epidermal growth factor was detected but below the quantification level with the chicken EGF ELISA kit. The microculture tetrazolium (MTT) assay was performed for growth stimulation assessment comparing human EGF and EBN. There was no significant cell growth observed in cancer cells after EBN treatment. In conclusion, EBN Malaysia has a good nutritional profile, free of heavy metals, and an acceptable level of nitrate, nitrite, and microorganism profile except for mould contents. Furthermore, the in vitro study indicated that EBN was not associated with cancer cell growth.
A healthy diet should nourish the brain with essential nutrients, including bioactive compounds, for normal brain functioning and to protect it from the negative effects of inflammation and oxidative stress. In this review, a concise summation of the protective effects of selected fruits, namely, berries, grapes, and citrus fruits, against neurological disorder is presented. The focus is on the neuroprotective potential of these fruits against neurodegenerative and mental disorders. The fruits selection was based on the vast reported pharmacological studies on their neuroprotection efficacies. Hence, the respective knowledge and limitations are discussed based on the biological and pharmacological evidence compiled from the previously reported laboratory, epidemiology, and intervention trials.
Objectives. To systematically review articles investigating the relationship between religion and spirituality (R/S) and fruit, vegetable, and fat intake. Methods. PubMed, CINAHL, and PsycInfo were searched for studies published in English prior to March 2013. The studies were divided into two categories: denominational studies and degree of R/S studies. The degree of R/S studies was further analyzed to (1) determine the categories of R/S measures and their relationship with fruit, vegetable, and fat intake, (2) evaluate the quality of the R/S measures and the research design, and (3) determine the categories of reported relationship. Results. Thirty-nine studies were identified. There were 14 denominational studies and 21 degree of R/S studies, and 4 studies were a combination of both. Only 20% of the studies reported validity and 52% reported reliability of the R/S measures used. All studies were cross-sectional, and only one attempted mediation analysis. Most studies showed a positive association with fruit and vegetable intake and a mixed association with fat intake. Conclusion. The positive association between R/S and fruit and vegetable intake may be one possible link between R/S and positive health outcome. However, the association with fat intake was mixed, and recommendations for future research are made.
Honey is one of the oldest substances used in wound management. Efficacy of Gelam honey in wound healing was evaluated in this paper. Sprague-Dawley rats were randomly divided into four groups of 24 rats each (untreated group, saline group, Intrasite Gel group, and Gelam honey group) with 2 cm by 2 cm full thickness, excisional wound created on neck area. Wounds were dressed topically according to groups. Rats were sacrificed on days 1, 5, 10, and 15 of treatments. Wounds were then processed for macroscopic and histological observations. Gelam-honey-dressed wounds healed earlier (day 13) than untreated and saline treated groups, as did wounds treated with Intrasite Gel. Honey-treated wounds exhibited less scab and only thin scar formations. Histological features demonstrated positive effects of Gelam honey on the wounds. This paper showed that Gelam honey dressing on excisional wound accelerated the process of wound healing.
Ylang-ylang (Cananga odorata Hook. F. & Thomson) is one of the plants that are exploited at a large scale for its essential oil which is an important raw material for the fragrance industry. The essential oils extracted via steam distillation from the plant have been used mainly in cosmetic industry but also in food industry. Traditionally, C. odorata is used to treat malaria, stomach ailments, asthma, gout, and rheumatism. The essential oils or ylang-ylang oil is used in aromatherapy and is believed to be effective in treating depression, high blood pressure, and anxiety. Many phytochemical studies have identified the constituents present in the essential oils of C. odorata. A wide range of chemical compounds including monoterpene, sesquiterpenes, and phenylpropanoids have been isolated from this plant. Recent studies have shown a wide variety of bioactivities exhibited by the essential oils and the extracts of C. odorata including antimicrobial, antibiofilm, anti-inflammatory, antivector, insect-repellent, antidiabetic, antifertility and antimelanogenesis activities. Thus, the present review summarizes the information concerning the traditional uses, phytochemistry, and biological activities of C. odorata. This review is aimed at demonstrating that C. odorata not only is an important raw material for perfume industry but also considered as a prospective useful plant to agriculture and medicine.
The antidiabetic potential of Alternanthera sessilis Red was investigated using the obese type 2 diabetic rats induced by high fat diet and streptozotocin. Three fractions (hexane, ethyl acetate, and water) were obtained from the crude ethanol extract of Alternanthera sessilis Red. Alternanthera sessilis Red ethyl acetate fraction (ASEAF) was found to possess the most potent antihyperglycemic effect through oral glucose tolerance test. The ASEAF was subsequently given to the diabetic rats for two weeks. It was found that two-week administration of ASEAF reduces the fasting blood glucose level, triglyceride level, and free fatty acid level of the rats. ASEAF-treated diabetic rats showed higher pancreatic insulin content and pancreatic total superoxide dismutase activity compared to the untreated diabetic rats. Also, the insulin sensitivity indexes suggested that ASEAF ameliorates the insulin resistant state of the diabetic rats. In conclusion, ASEAF could be developed into a potential antidiabetic agent for the management of type 2 diabetes.
Manilkara zapota (L.) P. Royen, called sapodilla, or locally known as ciku, belongs to the family Sapotaceae. We found that Manilkara zapota leaf water extract has cytotoxic effect against human hepatocellular carcinoma (HepG2) cell line in our earlier study. Therefore, this study aimed to explore the anticancer properties of Manilkara zapota leaf water extract in HepG2 cells. We also aimed to unravel yet undiscovered mechanisms and identified several expressed genes whose functions in cytotoxicity activity of Manilkara zapota leaf water extract in HepG2 cells have not been well-studied. The apoptosis and intracellular reactive oxygen species (ROS) activities were analyzed using Annexin V-propidium iodide staining and dichlorodihydrofluorescein diacetate, respectively, by NovoCyte Flow Cytometer. Bax and Bcl-2 expression were assessed using Enzyme-Linked Immunosorbent Assay. The associated molecular pathways were evaluated by quantitative real-time PCR. Overall analyses revealed that Manilkara zapota leaf water extract can increase percentage of early apoptotic cells, induce the formation of ROS, upregulate c-Jun N-terminal kinase 1 (JNK1) and inducible nitric oxide synthase (iNOS), and reduce Akt1 and vascular endothelial growth factor A (VEGFA) transcriptional activities. Our data suggest that Manilkara zapota leaf water extract can suppress the growth of HepG2 cells via modulation of ERK1/2/Akt1/JNK1 transcriptional expression.
Manilkara zapota (L.) P. Royen (family: Sapotaceae) is commonly called sapodilla, or locally known as ciku. The detailed mechanisms underlying Manilkara zapota leaf methanol extract against HeLa human cervical cancer cells have yet to be investigated. Therefore, our present study is designed to investigate the ability to induce apoptosis and the underlying mechanisms of Manilkara zapota leaf methanol extract inducing cytotoxicity in HeLa cells. The apoptotic cell death was assessed using Annexin V-propidium iodide staining. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential activities were measured using dichlorodihydrofluorescein diacetate and MitoLite Orange, respectively, by NovoCyte Flow Cytometer. Bax and Bcl-2 expression were evaluated using Enzyme-Linked Immunosorbent Assay. Caspase-3 activity was determined using a colorimetric assay. The associated biological interaction pathways were evaluated using quantitative real-time PCR. Our data showed that HeLa cells were relatively more sensitive to Manilkara zapota leaf methanol extract than other cancer cell lines studied. Overall analyses revealed that Manilkara zapota leaf methanol extract can inhibit the viability of HeLa cells, induce mitochondrial ROS generation, and inhibit nuclear factor-kappa B (NF-κB) and epidermal growth factor receptor (EGFR) transcriptional activities. Our results suggested that Manilkara zapota leaf methanol extract might represent a potential anticervical cancer agent.
The distribution patterns of flavonoids and cyclohexenyl chalcone derivatives in conventional propagated (CP) and in vitro-derived (CPA) field-grown plants of an important medicinal ginger, Boesenbergia rotunda, are described. A total of eight compounds were extracted from six organs (rootlet, rhizome, shoot base, maroon stem, stalk, and leaf) of the CP and CPA plants. Five major chromatographic peaks, namely, alpinetin, pinocembrin, pinostrobin, 4-hydroxypanduratin A, and panduratin A, were consistently observed by high performance liquid chromatography. Nonaerial organs had higher levels of flavonoids than the aerial ones for all types of samples. Among the compounds detected, pinostrobin and 4-hydroxypanduratin A were the most abundant flavonoid and cyclohexenyl chalcone derivative, respectively. The distribution and abundance of the bioactive compounds suggested that the shoot base could be more potentially useful for medicinal application than other organs of the plant and may be the site of storage or occurrence of biosynthetic enzymatic activities.
Testosterone replacement is the choice of treatment in androgen-deficient osteoporosis. However, long-term use of testosterone is potentially carcinogenic. Eurycoma longifolia (EL) has been reported to enhance testosterone level and prevent bone calcium loss but there is a paucity of research regarding its effect on the bone structural parameters. This study was conducted to explore the bone structural changes following EL treatment in normal and androgen-deficient osteoporosis rat model. Thirty-six male Sprague-Dawley rats aged 12 months were divided into normal control, normal rat supplemented with EL, sham-operated, orchidectomised-control, orchidectomised with testosterone replacement, and orchidectomised with EL supplementation groups. Testosterone serum was measured both before and after the completion of the treatment. After 6 weeks of the treatment, the femora were processed for bone histomorphometry. Testosterone replacement was able to raise the testosterone level and restore the bone volume of orchidectomised rats. EL supplementation failed to emulate both these testosterone actions. The inability of EL to do so may be related to the absence of testes in the androgen deficient osteoporosis model for EL to stimulate testosterone production.
Methanolic extract of Cynometra cauliflora whole fruit was assayed for cytotoxicity against the human promyelocytic leukemia HL-60 and the normal mouse fibroblast NIH/3T3 cell lines by using the MTT assay. The CD(50) of the extract for 72 hours was 0.9 μg/mL whereas the value for the cytotoxic drug vincristine was 0.2 μg/mL. The viability of the NIH/3T3 cells was at 80.0% when treated at 15.0 μg/mL. The extract inhibited HL-60 cell proliferation with dose dependence. AO/PI staining of HL-60 cells treated with the extract revealed that majority of cells were in the apoptotic cell death mode. Flow cytometry analysis of HL-60 cells treated at CD(50) of the extract showed that the early apoptotic cells were 31.0, 26.3 and 19.9% at 24, 48, and 72 hours treatment, respectively. The percentage of late apoptotic cells was increased from 62.0 at 24 hours to 64.1 and 70.2 at 48 and 72 hours, respectively. Meanwhile, percent of necrotic cells were 4.9, 6.6, and 8.5 at 24, 48, and 72 hours, respectively. This study has shown that the methanolic extract of C. cauliflora whole fruit was cytotoxic towards HL-60 cells and induced the cells into apoptotic cell death mode, but less cytotoxic towards NIH/3T3 cells.
Obesity has been often associated with the occurrence of cardiovascular diseases, type 2 diabetes, and cancer. The development of obesity is also accompanied by significant differentiation of preadipocytes into adipocytes. In this study, we investigated the activity of α-mangostin, a major xanthone component isolated from the stem bark of G. malaccensis, on glucose uptake and adipocyte differentiation of 3T3-L1 cells focusing on PPARγ, GLUT4, and leptin expressions. α-Mangostin was found to inhibit cytoplasmic lipid accumulation and adipogenic differentiation. Cells treated with 50 μM of α-mangostin reduced intracellular fat accumulation dose-dependently up to 44.4% relative to MDI-treated cells. Analyses of 2-deoxy-D-[(3)H] glucose uptake activity showed that α-mangostin significantly improved the glucose uptake (P < 0.05) with highest activity found at 25 μM. In addition, α-mangostin increased the amount of free fatty acids (FFA) released. The highest glycerol release level was observed at 50 μM of α-mangostin. qRT-PCR analysis showed reduced lipid accumulation via inhibition of PPARγ gene expression. Induction of glucose uptake and free fatty acid release by α-mangostin were accompanied by increasing mRNA expression of GLUT4 and leptin. These evidences propose that α-mangostin might be possible candidate for the effective management of obesity in future.
Bioassay-guided isolation of the active hexane fractions of Curcuma zedoaria led to the identification of five pure compounds, namely, curzerenone (1), neocurdione (2), curdione (3), alismol (4), and zederone (5) and a mixture of sterols, namely, campesterol (6), stigmasterol (7), and β -sitosterol (8). Alismol has never been reported to be present in Curcuma zedoaria. All isolated compounds except (3) were evaluated for their cytotoxic activity against MCF-7, Ca Ski, and HCT-116 cancer cell lines and noncancer human fibroblast cell line (MRC-5) using neutral red cytotoxicity assay. Curzerenone and alismol significantly inhibited cell proliferation in human cancer cell lines MCF-7, Ca Ski, and HCT-116 in a dose-dependent manner. Cytological observations by an inverted phase contrast microscope and Hoechst 33342/PI dual-staining assay showed typical apoptotic morphology of cancer cells upon treatment with curzerenone and alismol. Both compounds induce apoptosis through the activation of caspase-3. It can thus be suggested that curzerenone and alismol are modulated by apoptosis via caspase-3 signalling pathway. The findings of the present study support the use of Curcuma zedoaria rhizomes in traditional medicine for the treatment of cancer-related diseases. Thus, two naturally occurring sesquiterpenoids, curzerenone and alismol, hold great promise for use in chemopreventive and chemotherapeutic strategies.
A wide range of medicinal and aromatic plants (MAPs) have been explored for their essential oils in the past few decades. Essential oils are complex volatile compounds, synthesized naturally in different plant parts during the process of secondary metabolism. Essential oils have great potential in the field of biomedicine as they effectively destroy several bacterial, fungal, and viral pathogens. The presence of different types of aldehydes, phenolics, terpenes, and other antimicrobial compounds means that the essential oils are effective against a diverse range of pathogens. The reactivity of essential oil depends upon the nature, composition, and orientation of its functional groups. The aim of this article is to review the antimicrobial potential of essential oils secreted from MAPs and their possible mechanisms of action against human pathogens. This comprehensive review will benefit researchers who wish to explore the potential of essential oils in the development of novel broad-spectrum key molecules against a broad range of drug-resistant pathogenic microbes.
We investigated the effect of different solvents (ethyl acetate, methanol, acetone, and chloroform) on the extraction of phytoconstituents from Lantana camara leaves and their antioxidant and antibacterial activities. Further, GC-MS analysis was carried out to identify the bioactive chemical constituents occurring in the active extract. The results revealed the presence of various phytocompounds in the extracts. The methanol solvent recovered higher extractable compounds (14.4% of yield) and contained the highest phenolic (92.8 mg GAE/g) and flavonoid (26.5 mg RE/g) content. DPPH radical scavenging assay showed the IC50 value of 165, 200, 245, and 440 μg/mL for methanol, ethyl acetate, acetone, and chloroform extracts, respectively. The hydroxyl scavenging activity test showed the IC50 value of 110, 240, 300, and 510 μg/mL for methanol, ethyl acetate, acetone, and chloroform extracts, respectively. Gram negative bacterial pathogens (E. coli and K. pneumoniae) were more susceptible to all extracts compared to Gram positive bacteria (M. luteus, B. subtilis, and S. aureus). Methanol extract had the highest inhibition activity against all the tested microbes. Moreover, methanolic extract of L. camara contained 32 bioactive components as revealed by GC-MS study. The identified major compounds included hexadecanoic acid (5.197%), phytol (4.528%), caryophyllene oxide (4.605%), and 9,12,15-octadecatrienoic acid, methyl ester, (Z,Z,Z)- (3.751%).
This study evaluates the phytochemistry, antioxidant, and antimicrobial effects of Plectranthus amboinicus leaves extracted in different solvents. The methanol extract contained the highest total phenolic (94.37 ± 1.24 mg GAE/g) and flavonoid contents (26.90 ± 1.35 mg RE/g) and exhibited the highest DPPH scavenging activity (90.13 ± 3.32%) followed by the acetone extract (80.23 ± 3.26%) at 500 μg/mL concentration. Similarly, the highest ferric ion reduction potential (849.63 ± 30.95 μM of Fe (II)/g dry weight) was exhibited by the methanol extract followed by the acetone extract (695.92 ± 25.44 μM of Fe (II)/g dry weight). The methanol extract showed greater antimicrobial activity against all the tested pathogens (Bacillus subtilis, Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans). However, both hexane and acetone extracts failed to inhibit E. coli. S. aureus and C. albicans were more susceptible to all the extracts. Further, GC-MS analysis confirmed the occurrence of a total 46 phytocompounds in different solvent extracts. Some of the major compounds included carvacrol (37.7%), tetracontane (16.6%), squalene (15.6%), tetrapentacontane (13.7%), and Phytol (12.9%). In conclusion, extraction solvents influenced the recovery of phytocompounds and the highest pharmacological activities of the methanol extract could be correlated to the presence of additional bioactive compounds.