Anticancer effects of traditional Chinese herbs with phlegm-eliminating properties - An overview.

ETHONOPHARMACOLOGICAL RELEVANCE: Cancer is considered to be the second leading cause of human death. It is unsatisfactory that in the past decades, the treatment for cancer has not progressed as fast as it was expected, as only 50% of newly diagnosed patients could be cured even today. The development of cancer is a multifactorial process, involving tumor cells themselves, the interactions between tumor cells and their microenvironments, as well as the interactions between tumor cells and the host's immunity. Focusing on any single goal may bring limited benefits. AIM AND METHODS OF THE STUDY: Phlegm-eliminating herbs, which can reduce phlegm and eliminate pathological metabolites, are commonly used to treat cancer in China. However, the underlying molecular targets and efficacy of herbal medicines in cancer treatment still remain unclear. In this study, we reviewed the potential anticancer mechanisms of some phlegm-eliminating herbs and their active ingredients from the articles through such scientific databases as MEDLINE, PubMed, and Google Scholar. RESULTS: We found that the anticancer mechanisms of phlegm-eliminating herbs and ingredients include inducing apoptosis, anti-proliferation, preventing tumor invasion and metastasis, and reducing resistance to chemotherapy. In addition, some phlegm-eliminating herbs and their ingredients have anti-inflammatory and anti-metabolic syndrome effects. CONCLUSIONS: We suggest that the phlegm-eliminating herbs and ingredients are potential candidates for anticancer treatment and cancer prevention by playing a comprehensive role.

Therapeutic effect of Jinlongshe Granule () on quality of life of stage IV gastric cancer patients using EORTC QLQ-C30: A double-blind placebo-controlled clinical trial.

OBJECTIVE: To evaluate the impact of Jinlongshe Granule (, JLSG) on quality of life (QOL) of stage IV gastric cancer patients. METHODS: This randomized, double-blind and placebo-controlled clinical trial included 50 patients with advanced gastric cancer. They were equally randomized into a JLSG group and a placebo group. Patients in both groups received routine Chinese herbal decoctions according to Chinese medicine (CM) treatment based on syndrome differentiation. Patients in JLSG group received additional JLSG, and those in the placebo group received an additional placebo. In the JLSG group, 19 patients who completed the study were used for analysis. In the placebo group, finally the data of 20 patients who completed the study were used for analysis. The treatment course was at least 3 months, and the follow-up duration was at least 6 months in 5 interviews. Repeated measurements of the subscale items and individual items in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30) obtained at the 5 interviews were compared using different patient groups, changes over time and changes within one group over time independently to observe the tendency of changes in the scores. RESULTS: Using time as the variant, there was signifificant difference in 4 functional scales (physical, role, emotional and social, P<0.05), 3 symptom scales (fatigue, nausea and vomiting and pain,P<0.05) and a global health status/QOL scale (P<0.05) and 6 single symptoms dyspnoea (P>0.05), insomnia (P<0.05), appetite loss (P<0.05), constipation (P<0.05), diarrhea (P>0.05) and financial difficulties (P<0.05). There was also signifificant difference in these items between the two groups when the placebo group and group over time were used as variants (P<0.05 or P<0.01). CONCLUSION: Additional use of JLSG on the basis of routine CM treatment could improve the somatic function, role function, emotional function, social function, cognitive function and general QOL of patients with advanced gastric cancer, and relieve the symptoms of fatigue, nausea and vomiting, pain, loss of appetite and constipation.

Xiaotan Sanjie decoction attenuates tumor angiogenesis by manipulating Notch-1-regulated proliferation of gastric cancer stem-like cells.

AIM: To determine the underlying mechanisms of action and influence of Xiaotan Sanjie (XTSJ) decoction on gastric cancer stem-like cells (GCSCs). METHODS: The gastric cancer cell line MKN-45 line was selected and sorted by FACS using the cancer stem cell marker CD44; the stemness of these cells was checked in our previous study. In an in vitro study, the expression of Notch-1, Hes1, Vascular endothelial growth factor (VEGF), and Ki-67 in both CD44-positive gastric cancer stem-like cells (GCSCs) and CD44-negative cells was measured by Western blot. The effect of XTSJ serum on cell viability and on the above markers was measured by MTT assay and Western blot, respectively. In an in vivo study, the ability to induce angiogenesis and maintenance of GCSCs in CD44-positive-MKN-45- and CD44-negative-engrafted mice were detected by immunohistochemical staining using markers for CD34 and CD44, respectively. The role of XTSJ decoction in regulating the expression of Notch-1, Hes1, VEGF and Ki-67 was measured by Western blot and real-time polymerase chain reaction. RESULTS: CD44(+) GCSCs showed more cell proliferation and VEGF secretion than CD44-negative cells in vitro, which were accompanied by the high expression of Notch-1 and Hes1 and positively associated with tumor growth (GCSCs vs CD44-negative cells, 2.72 ± 0.25 vs 1.46 ± 0.16, P < 0.05) and microvessel density (MVD) (GCSCs vs CD44-negative cells, 8.15 ± 0.42 vs 3.83 ± 0.49, P < 0.001) in vivo. XTSJ decoction inhibited the viability of both cell types in a dose-dependent manner in vitro. Specifically, a significant difference in the medium- (82.87% ± 6.53%) and high-dose XTSJ groups (77.43% ± 7.34%) was detected at 24 h in the CD44(+) GCSCs group compared with the saline group (95.42% ± 5.76%) and the low-dose XTSJ group (90.74% ± 6.57%) (P < 0.05). However, the efficacy of XTSJ decoction was reduced in the CD44(-) groups; significant differences were only detected in the high-dose XTSJ group at 48 h (78.57% ± 6.94%) and 72 h (72.12% ± 7.68%) when compared with the other CD44- groups (P < 0.05). Notably, these differences were highly consistent with the Notch-1, Hes1, VEGF and Ki-67 expression in these cells. Similarly, in vivo, XTSJ decoction inhibited tumor growth in a dose-dependent manner. A significant difference was observed in the medium- (1.76 ± 0.15) and high-dose XTSJ (1.33 ± 0.081) groups compared with the GCSCs control group (2.72 ± 0.25) and the low-dose XTSJ group (2.51 ± 0.25) (P < 0.05). We also detected a remarkable decrease of MVD in the medium- (7.10 ± 0.60) and high-dose XTSJ (5.99 ± 0.47) groups compared with the GCSC control group (8.15 ± 0.42) and the low-dose XTSJ group (8.14 ± 0.46) (P < 0.05). Additionally, CD44 expression was decreased in these groups [medium- (4.43 ± 0.45) and high-dose XTSJ groups (3.56 ± 0.31) vs the GCSC control (5.96 ± 0.46) and low dose XTSJ groups (5.91 ± 0.38)] (P < 0.05). The significant differences in Notch-1, Hes1, VEGF and Ki-67 expression highly mirrored the results of XTSJ decoction in inhibiting tumor growth, MVD and CD44 expression. CONCLUSION: Notch-1 may play an important role in regulating the proliferation of GCSCs; XTSJ decoction could attenuate tumor angiogenesis, at least partially, by inhibiting Notch-1.

Xiaotan Tongfu granules contribute to the prevention of stress ulcers.

AIM: To investigate the efficacy and potential mechanism of Xiaotan Tongfu granules (XTTF) in stress ulcers. METHODS: One hundred sixty rats were randomly divided into 4 groups (n = 10) as follows: the model group (MP group), the control group (CP group), the ranitidine group (RP group) and the XTTF granule group (XP group). Rats in the MP group received no drugs, rats in the CP group received 0.2 mL of a 0.9% sodium chloride solution via oral gavage, and rats in the RP and XP groups received the same volume of ranitidine (50 mg/kg) or XTTF granule (4.9 g/kg). The cold-restraint stress model was applied to induce stress ulcers after 7 consecutive days of drug administration. Afterwards, rats were sacrificed at 0, 3, 6 and 24 h. Gastric pH was measured by a precise pH meter; gastric emptying rate (GER) was measured by using a methylcellulose test meal; myeloperoxidase activity (MPO), macrophage migration inhibitory factor (MIF), proliferating cell nuclear antigen (PCNA), and heat shock protein 70 (HSP70) were measured by immunohistochemical staining; and mucosal cell apoptosis was measured by transferase dUTP nick end labeling. RESULTS: In the cold-restraint stress model, the development of stress ulcers peaked at 3 h and basically regressed after 24 h. Gastric lesions were significantly different in the RP and XP groups at each time point. Interestingly, although this index was much lower in the RP group than in the XP group immediately following stress induction (7.00 ± 1.10 vs 10.00 ± 1.79, P < 0.05. Concerning gastric pH, between the RP and XP groups, we detected a statistically significant difference immediately after stress induction (0 h: 4.56 ± 0.47 vs 3.34 ± 0.28, P < 0.05) but not at any of the subsequent time points. For GER, compared to the RP group, GER was remarkably elevated in the XP group because a statistically significant difference was detected (3 h: 46.84 ± 2.70 vs 61.16 ± 5.12, P < 0.05; 6 h: 60.96 ± 6.71 vs 73.41 ± 6.16, P < 0.05; 24 h: 77.47 ± 3.17 vs 91.31 ± 4.34, P < 0.05). With respect to MPO and MIF, comparisons between the RP and XP groups revealed statistically significant differences at 3 h (MPO: 18.94 ± 1.20 vs 13.51 ± 0.89, P < 0.05; MIF: 150.67 ± 9.85 vs 122.17 ± 5.67, P < 0.05) and 6 h (MPO: 13.22 ± 1.54 vs 8.83 ± 0.65, P < 0.05; MIF: 135.50 ± 9.46 vs 109.83 ± 6.40, P < 0.05). With regard to HSP70, HSP70 expression was significantly increased in the RP and XP groups at 3 and 6 h compared to the MP and CP groups. In addition, comparing the RP and XP groups also showed statistically significant differences at 3 and 6 h. The expression of PCNA was higher in the RP and XP groups 3 h after stress induction. Between these two groups, small but statistically significant differences were observed at all of the time points (3 h: 69.50 ± 21.52 vs 79.33 ± 15.68, P < 0.05; 6 h: 107.83 ± 4.40 vs 121.33 ± 5.71, P < 0.05; 24 h: 125.33 ± 5.65 vs 128.50 ± 14.49, P < 0.05) except 0 h. With regard to apoptosis, the apoptotic activity in the RP and XP groups was significantly different from that in the MP and CP groups. The XP group exhibited a higher inhibition of cell apoptosis than the RP group at 3 h (232.58 ± 24.51 vs 174.46 ± 10.35, P < 0.05) and 6 h (164.74 ± 18.31 vs 117.71 ± 12.08, P < 0.05). CONCLUSION: The Xiaotan Tongfu granule was demonstrated to be similar to ranitidine in preventing stress ulcers. It exhibited multiple underlying mechanisms and deserves further study.

A chinese herbal formula to improve general psychological status in posttraumatic stress disorder: a randomized placebo-controlled trial on sichuan earthquake survivors.

Introduction. Posttraumatic stress disorder (PTSD) is accompanied by poor general psychological status (GPS). In the present study, we investigated the effects of a Chinese herbal formula on GPS in earthquake survivors with PTSD. Methods. A randomized, double-blind, placebo-controlled trial compared a Chinese herbal formula, Xiao-Tan-Jie-Yu-Fang (XTJYF), to placebo in 2008 Sichuan earthquake survivors with PTSD. Patients were randomized into XTJYF (n = 123) and placebo (n = 122) groups. Baseline-to-end-point score changes in the three global indices of the Symptom Checklist-90-Revised (SCL-90-R) and rates of response in the SCL global severity index (GSI) were the primary endpoints. A subanalysis of the nine SCL factors and the sleep quality score were secondary endpoints. Results and Discussion. Compared to placebo, the XTJYF group was significantly improved in all three SCL global indices (P = 0.001~0.028). More patients in the XTJYF group reported "much improved" than the placebo group (P = 0.001). The XTJYF group performed significantly better than control in five out of nine SCL factors (somatization, obsessive-compulsive behavior, depression, anxiety, and hostility (P = 0.001~0.036)), and in sleep quality score (P < 0.001). XTJYF produced no serious adverse events. These findings suggest that XTJYF may be an effective and safe treatment option for improving GPS in patients with PTSD.

[Effects of Xiaotan Sanjie Decoction-containing serum on proliferation and apoptosis of human gastric cancer cells MKN-45].

OBJECTIVE: To observe the effects of serum containing Xiaotan Sanjie Decoction, a compound traditional Chinese herbal medicine, on proliferation and apoptosis of human gastric cancer cell line MKN-45. METHODS: After coculturing MKN-45 cells with low-, medium- and high-dose Xiaotan Sanjie Decoction-containing serum, inverted microscope was utilized to observe morphological changes and counting chamber was used to count the MKN-45 cells; the proliferation of MKN-45 cells was determined by cell counting kit 8; Annexin V-fluorescein isothiocyanate/propidium iodide double label method was used to detect apoptosis rate of MKN-45 cells. RESULTS: Xiaotan Sanjie Decoction-containing serum significantly inhibited the proliferation of MKN-45 cells. The typical morphological changes of apoptotic MKN-45 cells were observed after treating with Xiaotan Sanjie Decoction-containing serum. The cell apoptosis was also observed by flow cytometry and the apoptosis rates of medium- and high-dose Xiaotan Sanjie Decoction-containing serum groups were higher than that of low-dose group. CONCLUSION: Xiaotan Sanjie Decoction-containing serum can inhibit the MKN-45 cell proliferation and induce cell apoptosis, which provides an experimental evidence for its treatment of human gastric cancer.

Study on analgesic effect of traditional Chinese medicine.

Chinese medicine has been used in treating pain for a long time. Much progress has been made in studies on the mechanism of the analgesic effect of Chinese medicine in animal experiments. It is found that the analgesic action may be related to the following actions: (1) Reducing the secretion of peripheral algogenic substances and inducing the secretion of pain-sensitive substances; (2) Alleviating the accumulation of local algogenic substances; (3) Increasing the release of endogenous analgesic substances; (4) Regulating c-fos gene and increasing the secretion of such substances in the central nervous system, etc. In this paper, the experimental methods and analgesic effect of Chinese medicines are reviewed.

Anticancer effect of jinlongshe granules on in situ-transplanted human MKN-45 gastric cancer in nude mice and xenografted sarcoma 180 in Kunming mice and its mechanism.

AIM: To study the antitumor effect of Chinese compound jinlongshe (JLS) granules on sarcoma 180 and MKN-45 human gastric cancer cell lines in vivo and its mechanism. METHODS: After establishment of S180 sarcoma (S180) and MKN-45 gastric cancer model of nude mice, the tumor-bearing mice were divided into 5 groups at random. Three experimental groups were respectively given the aqueous extract of JLS granules at doses of 120 g, 60 g and 20 g/(kg per 6/wk, i.g.) for 3 wk in S180 and 6 wk in nude mice model. Positive control was given cyclophosphamide (Cy) at a dose of 50 mg/(kg per 3/wk, i.g.) for 3 wk in S180 models and 5-Fluorouracil (5-FU) 20 mg/(kg per 3/wk, i.g.) for 3 wk in nude mice model. Negative control was given normal saline (NS) at a dose of 0.18 g/(kg per 6/wk, i.g.) respectively. After 3 wk in mice bearing S180 tumor and 6 wk in nude mice model, the experimental animals were sacrificed and the masses of tumor were weighed, and the rates of tumor inhibition of each treated group were calculated respectively. To determine the antitumor mechanisms, the morphological changes, cell cycle and apoptosis were observed in MKN-45 nude mice model. Annexin V-FITC/PI double staining FCM assay was used to further determine the live cells, apoptotic cells, necrotic cells and debris. RESULTS: The inhibitory rates of JLS granules at the doses of 20 g/kg, 60 g/kg and 120 g/kg were 50.31%, 55.94% and 68.13% (P < 0.01) in nude mice models and 40.90%, 50.32% and 58.46% (P < 0.01) in S180 model. The inhibitory rate of Cy was 85.22% in S180 models and the inhibitory rate of 5-FU was 53.43% in nude mice model (P < 0.01). Nuclear chromatin and margination were observed under a transmission electron microscope (TEM). The G0/G1 phase was arrested, typical apoptotic peak appeared, the apoptotic rate was 22.81%-38.54% in three JLS granule-treated groups. Annexin V-FITC/PI double staining FCM assay showed that the apoptotic cells were 4.36%, 3.08% and 7.08% in three dosages, most cells were localized in the low right quadrant. CONCLUSION: Jinlongshe granules possess anti-tumor effects on experimental tumor models in vivo, and apoptosis induction is one of its anti-tumor mechanisms.

[Effects of jinlongshe granules on apoptosis of MKN-45 human gastric cancer cells orthotopically transplanted in nude mice].

OBJECTIVE: To assess the effects of Jinlongshe Granules (JLSG) on tumor growth of gastric carcinoma. METHODS: Fifty nude mice orthotopically transplanted with MKN-45 human gastric cancer cells were divided into five groups: untreated group, 5-fluorouracil (5-FU)-treated group and high-, medium-, and low-dose JLSG-treated groups. Corresponding antitumor drugs were administered in each group except the untreated group. The antitumor effects in vivo were evaluated. Cell cycle distribution and apoptosis of MKN-45 human gastric cancer cells were determined by using flow cytometry (FCM) and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining assay. The ultrastructure of MKN-45 gastric cancer cells was observed by transmission electron microscope. RESULTS: In the mice treated with high-, medium-, and low-dose JLSG, the growth inhibition rates of gastric cancer were 68.13%, 55.94% and 50.31% respectively, and this antitumor effect was dose-dependent. In the mice treated with intraperitoneal injection of 5-FU, the growth inhibition rate of gastric cancer was 53.43% and not much different from those treated with JLSG. The apoptotic rates in the high-, medium-, and low-dose JLSG-treated groups were 22.81%, 28.27% and 38.54% respectively, in a dose-dependent manner, with the cell cycle arrested at G(0)/G(1) phase. An Annexin V-FITC/PI staining assay revealed that the percentages of early apoptotic cells in the three dose JLSG-treated groups were all significantly higher than that in the 5-FU-treated group, whereas the late apoptotic and necrotic cells were much more in the 5-FU-treated group than those in the three dose JLSG-treated groups. CONCLUSION: Jinlongshe Granules exert an inhibiting effect on MKN-45 human gastric cancer cell.