The Fruits of Paris polyphylla Inhibit Colorectal Cancer Cell Migration Induced by Fusobacterium nucleatum-Derived Extracellular Vesicles.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Gut microbiota are highly associated with CRC, and Fusobacterium nucleatum was found to be enriched in CRC lesions and correlated with CRC carcinogenesis and metastases. Paris polyphylla is a well-known herbal medicine that showed anticancer activity. The present study demonstrates that P. polyphylla inhibited the growth of CRC cells. In addition, treating with active compounds pennogenin 3-O-beta-chacotrioside and polyphyllin VI isolated from P. polyphylla inhibited the growth of F. nucleatum. We also found that extracellular vesicles (EVs) released from F. nucleatum could promote mitochondrial fusion and cell invasion in CRC cells, whereas active components from P. polyphylla could dampen such an impact. The data suggest that P. polyphylla and its active ingredients could be further explored as potential candidates for developing complementary chemotherapy for the treatment of CRC.

Taiwanofungus camphoratus Combined With Amphotericin B for Metastatic Cancer Patients Unresponsive to or Unwilling to Undergo Chemotherapy: A Pilot Study.

CONTEXT: Taiwanofungus camphoratus is a parasitic mushroom found in the heartwood of Cinnamomum kanehirai and is used as a nutritional supplement. It has an anticancer action, both alone and synergistically with amphotericin B (AmB). OBJECTIVE: The study intended to assess the efficacy of a T camphoratus ethanol extract (TCEE) combined with AmB for patients with metastatic cancer whose cancer did not respond to multiline chemotherapy or who were unwilling to receive chemotherapy. DESIGN: The research team performed a retrospective analysis as a pilot study. SETTING: The study took place at a single hospital (Taipei Medical University Hospital, Taipei, Taiwan). PARTICIPANTS: Participants were 9 patients at the hospital who were terminally ill with metastatic cancer. INTERVENTIONS: The participants had received daily doses of 2-3 g of the TCEE in combination with a weekly dose of 20-25 mg of AmB in 500 cc of 5% glucose water, given intravenously in 4-6 h. OUTCOME MEASURES: Outcome measures included (1) a primary evaluation index measuring the efficacy of the treatment; (2) a measure of tumor burden that was estimated using the response evaluation criteria in solid tumors (RECIST 1.1), (3) a secondary evaluation index measuring survival duration, and (4) safety. RESULTS: The mean treatment time was 54.4 ± 18.3 wk. At the end of the study, 2 patients showed a continued complete response, 1 patient had a continued partial response, and 1 patient showed a stable disease. The other 5 participants had times to progression ranging from 24 to 48 wk, with a mean of 35.6 wk. The mean survival time was 57.8 ± 18.5 wk, and 5 patients were still alive at the end of the study. CONCLUSIONS: For patients whose metastatic cancer did not respond to multiline chemotherapy or who were unwilling to receive chemotherapy, the use of TCEE as an adjuvant therapy to AmB resulted in tumor suppression and a delay in time to disease progression. The preliminary results reported here can be used to guide a future, more extensive clinical study of the combination.

Paris Polyphylla Inhibits Colorectal Cancer Cells via Inducing Autophagy and Enhancing the Efficacy of Chemotherapeutic Drug Doxorubicin.

Colorectal cancer is one of the most common cancers worldwide and chemotherapy is the main approach for the treatment of advanced and recurrent cases. Developing an effective complementary therapy could help to improve tumor suppression efficiency and control adverse effects from chemotherapy. Paris polyphylla is a folk medicine for treating various forms of cancer, but its effect on colorectal cancer is largely unexplored. The aim of the present study is to investigate the tumor suppression efficacy and the mechanism of action of the ethanolic extract from P. polyphylla (EEPP) in DLD-1 human colorectal carcinoma cells and to evaluate its combined effect with chemotherapeutic drug doxorubicin. The data indicated that EEPP induced DLD-1 cell death via the upregulation of the autophagy markers, without triggering p53- and caspase-3-dependent apoptosis. Moreover, EEPP treatment in combination with doxorubicin enhanced cytotoxicity in these tumor cells. Pennogenin 3-O-beta-chacotrioside and polyphyllin VI were isolated from EEPP and identified as the main candidate active components. Our results suggest that EEPP deserves further evaluation for development as complementary chemotherapy for colorectal cancer.

Applications of Pueraria lobata in treating diabetics and reducing alcohol drinking.

Pueraria lobata is one of the most important medicinal herbs used traditionally in China. According to Shanghan Lun (Treatise on Exogenous Febrile Disease), it has been used traditionally to relieve body heat, eye soring, dry mouth, headache associated with high blood pressure, and stiff neck problems. Modern studies in the 1970s revealed that isoflavonoids extracted from P. lobata were the bioactive components of an herbal remedy namely Yufeng Ningxin Tablets for the treatment of patients after stroke. This article reviews recent application of P. lobota in the treatment of diabetics and in reducing alcohol drinking. In view of its low toxicity profile, P. lobota stands an excellent chance to be developed as a phytomedicine for treating human diseases.

Inhibition of aqueous extracts of Solanum nigrum (AESN) on oral cancer through regulation of mitochondrial fission.

The present study is designed to investigate the anti-oral cancer properties of Solanum nigrum on oral squamous cell carcinoma. S. nigrum is a Chinese herb used for suppression of various cancers. However, the inhibition of S. nigrum on oral cancer is unclear. Therefore, human oral squamous cancer cells (SCC)-4 were used to evaluate the effect of aqueous extracts of S. nigrum (AESN) on cancer cell proliferation, cell cycle, mitochondrial function and apoptosis. The SCC-4 cells were treated by AESN to evaluate the inhibition of cell proliferation and mitochondrial function in vitro. Our results suggested that AESN markedly increased reactive oxygen species production. AESN also promoted caspase-9 and caspase-3 activation and subsequent triggering of the mitochondrial apoptotic pathway. The inhibition of glucose uptake was alleviated mediated by a dose-dependent manner in SCC-4 cells with AESN treatment for 24 h, resulting in mitochondrial fission. These results suggested that AESN has potential to be used as a functional food in adjuvant chemotherapy for treating human oral cancer by suppression of mitochondrial function.

Aqueous Extract of Paris polyphylla (AEPP) Inhibits Ovarian Cancer via Suppression of Peroxisome Proliferator-Activated Receptor-Gamma Coactivator (PGC)-1alpha.

Chemotherapy, a major approach was used in carcinoma treatment, always involves the development of drug resistance as well as side-effects that affect the quality of patients' lives. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance was established recently. We demonstrate in this paper that the aqueous extract of Paris polyphylla (AEPP)-a traditional Chinese medicine-can be used in various cancer types for suppression of carcinogenesis. We evaluated the suppressions of EMT and mitochondrial activity by AEPP treatment in a high-glucose (HG) induced-human ovarian carcinoma cell line (OVCAR-3 cells). The mitochondrial morphology was investigated using MitoTracker Deep Red FM staining. Our results indicated that AEPP reduced the viability of OVCAR-3 cells considerably through induction of apoptosis. However, this inhibitory potential of AEPP was attenuated by HG induction in OVCAR-3 cells. The levels of estrogen-related receptor (ERR)-alpha activator and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha were elevated by HG induction, but were suppressed by AEPP treatment. Down-regulations of cell survival and EMT were oberved in OVCAR-3 cells through suppression of PGC-1alpha by AEPP treatment. These results were confirmed through PGC-1alpha knockdown and overexpression in OVCAR-3 cells. Thus, AEPP can be beneficial for treating ovarian cancer and has potential for development of an integrative cancer therapy against ovarian cancer proliferation, metastasis, and migration.

Anti-Cancer Activity of Solanum nigrum (AESN) through Suppression of Mitochondrial Function and Epithelial-Mesenchymal Transition (EMT) in Breast Cancer Cells.

Chemotherapy is the main approach for treating advanced and recurrent carcinoma, but the clinical performance of chemotherapy is limited by relatively low response rates, drug resistance, and adverse effects that severely affect the quality of life of patients. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance has been investigated in recent studies. Our recent studies have found that the aqueous extract of Solanum nigrum (AESN) is a crucial ingredient in some traditional Chinese medicine formulas for treating various types of cancer patients and exhibits antitumor effects. We evaluated the suppression of EMT in MCF-7 breast cancer cells treated with AESN. The mitochondrial morphology was investigated using Mitotracker Deep-Red FM stain. Our results indicated that AESN markedly inhibited cell viability of MCF-7 breast cancer cells through apoptosis induction and cell cycle arrest mediated by activation of caspase-3 and production of reactive oxygen species. Furthermore, mitochondrial fission was observed in MCF-7 breast cancer cells treated with AESN. In addition to elevation of E-cadherin, downregulations of ZEB1, N-cadherin, and vimentin were found in AESN-treated MCF-7 breast cancer cells. These results suggested that AESN could inhibit EMT of MCF-7 breast cancer cells mediated by attenuation of mitochondrial function. AESN could be potentially beneficial in treating breast cancer cells, and may be of interest for future studies in developing integrative cancer therapy against proliferation, metastasis, and migration of breast cancer cells.

Solanum nigrum Protects against Hepatic Fibrosis via Suppression of Hyperglycemia in High-Fat/Ethanol Diet-Induced Rats.

BACKGROUND: Advanced glycation end products (AGEs) signal through the receptor for AGE (RAGE), which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN) on AGEs-induced RAGE signaling and activation of hepatic stellate cells (HSCs) and hyperglycemia induced by high-fat diet with ethanol. METHODS: An animal model was used to evaluate the anti-hepatic fibrosis activity of AESN in rats fed a high-fat diet (HFD; 30%) with ethanol (10%). Male Wistar rats (4 weeks of age) were randomly divided into four groups (n = 6): (1) control (basal diet); (2) HFD (30%) + ethanol (10%) (HFD/ethanol); (3) HFD/ethanol + AESN (100 mg/kg, oral administration); and (4) HFD/ethanol + pioglitazone (10 mg/kg, oral administration) and treated with HFD for 6 months in the presence or absence of 10% ethanol in dietary water. RESULTS: We found that AESN improved insulin resistance and hyperinsulinemia, and downregulated lipogenesis via regulation of the peroxisome proliferator-activated receptor α (PPARα), PPARγ co-activator (PGC-1α), carbohydrate response element-binding protein (ChREBP), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) mRNA levels in the liver of HFD/ethanol-treated rats. In turn, AESN may delay and inhibit the progression of hepatic fibrosis, including α-smooth muscle actin (α-SMA) inhibition and MMP-2 production. CONCLUSIONS: These results suggest that AESN may be further explored as a novel anti-fibrotic strategy for the prevention of liver disease.

Miracle Fruit (Synsepalum dulcificum) Exhibits as a Novel Anti-Hyperuricaemia Agent.

Miracle fruit (Synsepalum dulcificum) belongs to the Sapotaceae family. It can change flavors on taste buds, transforming acidic tastes to sweet. We evaluated various miracle fruit extracts, including water, butanol, ethyl acetate (EA), and hexane fractions, to determine its antioxidant effects. These extracts isolated from miracle fruit exerted potential for reduction of uric acid and inhibited xanthine oxidase activity in vitro and in monosodiumurate (MSU)-treated RAW264.7 macrophages. Moreover, we also found that the butanol extracts of miracle fruit attenuated oxonic acid potassium salt-induced hyperuricaemia in ICR mice by lowering serum uric acid levels and activating hepatic xanthine oxidase. These effects were equal to those of allopurinol, suggesting that the butanol extract of miracle fruit could be developed as a novel anti-hyperuricaemia agent or health food.

Antioxidant activity and delayed aging effects of hot water extract from Chamaecyparis obtusa var. formosana leaves.

The antioxidant activity and delayed aging effects of hot water extracts from leaves of Chamaecyparis obtusa var. formosana were investigated. Free radical, superoxide radical scavenging, and total phenolic content assays were employed to evaluate the in vitro activities of the extracts. In addition, in vivo assays using the nematode Caenorhabditis elegans were also performed in this study. The results showed that among all soluble fractions obtained from the extracts, the ethyl acetate-soluble fraction has the best in vitro and in vivo antioxidant activities. Moreover, it decreased significantly the deposition of lipofuscin (aging pigment) and extended the lifespan of C. elegans. Bioactivity-guided fractionation yielded six potent antioxidant constituents from the ethyl acetate-soluble fraction, namely, catechin, quercetin, quercetin-3-O-α-rhamnoyranoside, myricetin-3-O-α-rhamnoyranoside, vanillic acid, and 4-hydroxybenzoic acid. Quercetin-3-O-α-rhamnoyranoside pretreatment showed the highest survival of C. elegans upon juglone exposure. Taken together, the results revealed that hot water extracts from C. obtusa var. formosana leaves have the potential to be used as a source for antioxidant or delayed aging health food.

Protective efficacy of selenite against lead-induced neurotoxicity in Caenorhabditis elegans.

BACKGROUND: Selenium is an essential micronutrient that has a narrow exposure window between its beneficial and toxic effects. This study investigated the protective potential of selenite (IV) against lead (Pb(II))-induced neurotoxicity in Caenorhabditis elegans. PRINCIPAL FINDINGS: The results showed that Se(IV) (0.01 µM) pretreatment ameliorated the decline of locomotion behaviors (frequencies of body bends, head thrashes, and reversal ) of C. elegans that are damaged by Pb(II) (100 µM) exposure. The intracellular ROS level of C. elegans induced by Pb(II) exposure was significantly lowered by Se(IV) supplementation prior to Pb(II) exposure. Finally, Se(IV) protects AFD sensory neurons from Pb(II)-induced toxicity. CONCLUSIONS: Our study suggests that Se(IV) has protective activities against Pb(II)-induced neurotoxicity through its antioxidant property.

Antihypertriglyceridemia and anti-inflammatory activities of monascus-fermented dioscorea in streptozotocin-induced diabetic rats.

The rice fermented by Monascus, called red mold rice (RMR), and has a long tradition in East Asia as a dietary staple. Monascus-fermented dioscorea called red mold dioscorea (RMD) contains various metabolites to perform the ability of reducing oxidative stress and anti-inflammatory response. We used Wistar rats and induced diabetes by injecting streptozotocin (STZ, 65 mg/kg i.p.). RMD was administered daily starting six weeks after disease onset. Throughout the experimental period, significantly (P < .05) lowered plasma glucose, triglyceride, cholesterol, free fatty acid and low density lipoprotein levels were observed in the RMD-treated groups. The RMD-treated diabetic rats showed higher activities of glutathione disulfide reductase, glutathione reductase, catalase and superoxide dismutase (P < .05) in the pancreas compared with the diabetic control rats. RMD also inhibited diabetes-induced elevation in the levels of interleukin (IL)-1ß, IL-6, interferon-γ and tumor necrosis factor-α. Pancreatic ß-cells damaged by STZ in the RMD supplemented groups were ameliorated. The results of this study clearly demonstrated that RMD possesses several treatment-oriented properties, including the control of hyperglycemia, antioxidant effects, pancreatic ß-cell protection and anti-inflammatory effects. Considering these observations, it appears that RMD may be a useful supplement to delay the development of diabetes and its complications.

Antioxidant and pancreas-protective effect of red mold fermented products on streptozotocin-induced diabetic rats.

BACKGROUND: Red mold fermented products contain various antioxidants, and were mentioned in an ancient Chinese pharmacopoeia of medicinal food and herbs. They were considered useful for the treatment of diabetes. The objective of this study was to determine the antioxidant and pancreas-protective function of red mold fermented products on streptozotocin (STZ)-induced diabetic rats. RESULTS: Throughout the experimental period (8 weeks), significantly (P < 0.05) lowered plasma glucose, amylase, triglyceride and cholesterol levels were observed in groups treated with red mold fermented products. Diabetic rats showed higher reactive oxygen species (P < 0.05) and lower activities of glutathione disulfide reductase, glutathione reductase and catalase (P < 0.05) in pancreas as compared to normal rats and those treated with red mold fermented products. There were some necrotic cells observed in the pancreas of diabetic rats and pancreatic tissue damaged by STZ in the red mold fermented products supplemented groups was ameliorated. CONCLUSION: These results indicate that red mold fermented products not only regulate hyperglycemia but also provide prevention against the effects of STZ-induced pancreatic damage.