Research progress in anti-colorectal cancer mechanism of berberine / 药学学报

Colorectal cancer (CRC) is a common malignancy burdening people globally, with increasing morbidity and mortality nowadays, due to the alternation in the diet type and lifestyle in modern society. Berberine, a type of benzylisoquinoline alkaloid, is widely present in numerous medicinal plants, particularly including Coptidis Rhizoma. Mounting evidence reveals that berberine possesses an array of pharmacological effects, such as anti-inflammation, anti-bacterium, anti-cancer, anti-diabetes mellitus and so on. In particular, berberine exhibits substantial inhibition on various types of cancers including CRC. Hereby, we sought to systematically review the suppressive effect of berberine on CRC through the diminishment of the proliferation and metastasis, induction of apoptosis, arrest of cell cycle, regulation of inflammatory reaction, the reverse of chemotherapeutic resistance and restoration of gut microbiota in CRC, so as to shed light on the in-depth mechanisms underlying the treatment of CRC with berberine in the clinical setting.

Research advances in phytochemistry, pharmacology and toxicology of oleanolic acid / 中国药理学与毒理学杂志

Oleanolic acid (OA) is a pentacyclic triterpenoid chemical component that exists in natural plants with a molecular formula of C30H48O3 and a molecular weight at 456.71 g·mol-1. OA is widespread in traditional Chinese herbal medicine (Ligustri Lucidi Fructus, Achyranthis Bidentate Radix, Red Sage) and berries (blueberries, grapes). In recent years, because of the extensive pharmacological effects of OA, its advantages in disease treatment have become increasingly prominent and gradually attracted the attention of pharmaceutical researchers. OA has effective therapeutic effects on a series of chronic diseases such as inflammation, cancer, diabetes, and cardiovascular diseases through mul?tiple signaling pathways and various targets. Especially in cancers, such as colorectal cancer, liver cancer, gastric cancer, lung cancer, breast cancer and other malignancies, OA presents substantial efficacy. However, its poor aqueous solubility, needy bioavailability, and unsatisfactory pharmacological activity excessively restrict its clinical application. More impor?tantly, the improper utilization of OA can cause adverse reactions, toxic effects and even damage to organs in some spe?cific situations. With the discovery of various pharmacological effects, the complex action mechanisms of OA, the contin?uous progress in structural modification of OA, as well as the synthesis of OA derivatives, its application is expand?ing gradually. Among numerous studies, there is a clear indication that OA and its derivatives, if fully developed, may provide an alternative and cheaper treatment for a variety of chronic diseases. However, the specific molecular mecha?nisms of OA and its derivatives as an alternative therapy and supplementary therapy for cancer, diabetes, cardiovascular disease and other chronic diseases remain to be clarified. Therefore, it is necessary to further study the pharmacokinet?ics, pharmacological activity, specific targets and related mechanisms of OA to lay a solid foundation for drug devel?opment and the application of OA in clinical settings.

Observations on the Efficacy of Heat-sensitive Point Medicinal Moxibustion plus Percutaneous Administration of Tetrandrine in Treating Lumbar Intervertebral Disc Herniation / 上海针灸杂志

Objective To investigate the clinical efficacy of heat-sensitive point medicinal moxibustion plus percutaneous administration of tetrandrine in treating lumbar intervertebral disc herniation. Methods One hundred and twenty patients with lumbar intervertebral disc herniation were randomized to treatment and control groups, 60 cases each. The treatment group received heat-sensitive point medicinal moxibustion plus percutaneous administration of tetrandrine and the control group, heat-sensitive point medicinal moxibustion alone. The VAS score and the JOA Score for Back Pain score were recorded in the two groups before and after treatment. The clinical therapeutic effects were compared between the two groups. Results There were statistically significant pre-/post-treatment differences in the JOA Score for Back Pain score and the VAS score in the two groups (P<0.01). There were statistically significant post-treatment differences in the JOA Score for Back Pain score and the VAS score between the treatment and control groups (P<0.01). The excellent and good rate was 80.0％ in the treatment group and 55.0％ in the control group; there was a statistically significant difference between the two groups (P<0.01). Conclusion Heat-sensitive point medicinal moxibustion plus percutaneous administration of tetrandrine is an effective way to treat lumbar intervertebral disc herniation.

Effects of Weipixiao (胃痞消) on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effects of Weipixiao (胃痞消, WPX) on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions (GPL).</p><p><b>METHODS</b>Sprague Dawley rats were randomly divided into control, model, vitacoenzyme (0.2 g·kg(-1)·day(-1)), WPX high-dose (H-WPX, 15 g·kg(-1)·day(-1)), WPX medium-dose (M-WPX, 7.5 g·kg(-1)·day(-1)) and WPX low-dose (L-WPX, 3.75 g·kg(-1)·day(-1)) groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-proteincoupled receptor 5 (Lgr5), matrix metalloproteinase-7 (MMP-7), Wnt1, Wnt3a, and β-catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software.</p><p><b>RESULTS</b>Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wnt1, Wnt3a and β-catenin than those of the control group(P<0.01). Interestingly, we also observed Lgr5+ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wnt1, and β-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups (P<0.05). A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups (P>0.05).</p><p><b>CONCLUSION</b>Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wnt1, β-catenin and the aberrant activation of Wnt/β-catenin pathway.</p>

The effect of baicalin on human brain microvascular endothelial cell under the glucose deprivation combined with hypoxia condition / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the mechanisms of baicalin on anti-cerebral ischemic through observing the effect of baicalin on human brain microvascular endothelial cell under the glucose deprivation combined with hypoxia condition.</p><p><b>METHODS</b>Human brain microvascular endothelial cells (HBMVECs) cultured in vitro were divided into the following groups: normal group, model group, baicalin high dose group, baicalin middle dose group, baicalin low dose group, nimodipine group. The kits were used to detect the cell viability, leakage rate of lactate dehydrogenase (LDH), Na(+)-K(+)-ATPase, Ca(2+)-ATPase, the concentration of Ca2+ in each group, and apoptosis rates of each group were analyzed by flow cytometry (FCM).</p><p><b>RESULTS</b>Compared with the normal group, the cell viability, Na(+)-K(+)-ATPase and Ca(2+)-ATPase in model group decreased significantly (P < 0.01, P < 0.05). But the leakage rate of LDH, Ca2+ in cells and apoptosis rates increased remarkably (P < 0.01). Compared with the model group, the cell viability, Na(+)-K(+)-ATPase and Ca(2+)-ATPase increased obviously (P < 0.01, P < 0.05) in baicalin high dose group. But the leakage rate of LDH and Ca2+ in cells in baicalin high dose group decreased significantly comparing with that of model group (P < 0.05, P < 0.01). And the reduction of intracellular Ca2+ was superior to that of nimodipine group. Meanwhile, the apoptosis rates decreased significantly in both baicalin high and middle dose groups (P < 0.01).</p><p><b>CONCLUSION</b>Baicalin could improve the cell viability of HBMVECs under the glucose deprivation combined with hypoxia condition. And the mechanisms were related with improving the energy metabolism, inhibiting intracellular calcium overload and decreasing the apoptosis rate of cells further.</p>

Comparative study on fMRI of the brain based on Dicang (ST 4), Hegu (LI 4) and Houxi (SI 3) on human body / 中国针灸

<p><b>OBJECTIVE</b>To observe the correlation relationship between acupuncture at Dicang (ST 4), Hegu (LI 4) and Houxi (SI 3) on the affected side of peripheral facial paralysis patients and activated areas in brain functional areas and central regulation mechanism of acupuncture at Hegu (LI 4) treatment.</p><p><b>METHODS</b>Eighteen cases with left peripheral facial paralysis were randomly divided into a Hegu group, a Dicang group and a Houxi group, 6 cases in each group. They were treated with electroacupuncture at left Dicang (ST 4), Hegu (LI 4) and Houxi (SI 3), respectively, and were examined with fMRI covering the whole brain at the same time. The fMRI data was analyzed by SPM software.</p><p><b>RESULTS</b>It was found that the left precentral gyrus area and the left postcentral gyrus area were activated when electroacupuncture at left Hegu (LI 4), and the right precentral gyrus area and the bilateral postcentral gyrus area were activated when electroacupuncture at left Dicang (ST 4), and there was no activated area at precentral gyrus area and post central gyrus area when electroacupuncture at left Houxi (SI 3).</p><p><b>CONCLUSION</b>The sensory importation information from Hegu (LI 4) and Dicang (ST 4) can converge and coincide in the brain and may influence each other.</p>

Effect of serum from overfatigue rats on JNK/c-Jun/HO-1 pathway in human umbilical vein endothelial cells and the intervening effect of Tongxinluo superfine powder / 中国结合医学杂志

<p><b>OBJECTIVE</b>To cultivate human umbilical vein endothelial cells (HUVECs) in the serum of overfatigue rats with the intervention of Tongxinluo superfine powder (TXLSP). By examining the variation of the activity of JNK/c-Jun/HO-1 pathway, the possible mechanisms of vascular endothelial dysfunction under overfatigue conditions and the intervening effect of TXLSP were explored.</p><p><b>METHODS</b>The HUVECs were randomly divided into the normal control group, the model group, the SP600125 (a specific antagonist of JNK) group, the TXLSP group and the TXLSP + SP600125 group. The content of carboyhemoglobin (COHb) and the leak rate of lactic dehydrogenase (LDH) in different groups were measured. The mRNA and protein expression of JNK, c-Jun, HO-1 and the phosphorylation level of c-Jun (P-c-Jun) were detected using Western blot and PCR methods.</p><p><b>RESULTS</b>Compared with the normal control group, the COHb level in supernatant was increased significantly in the model group, and the expression of HO-1, JNK, c-Jun mRNA and corresponding proteins and P-c-Jun were also increased remarkably. The increases in these parameters were significantly decreased by SP600125. TXLSP showed remarkable up-regulation on the expression of JNK, c-Jun, P-c-Jun and HO-1 mRNA and their protein expression. Compared with the SP600125 group, the expressions of JNK, c-Jun, P-c-Jun and HO-1 mRNA and its protein in the TXLSP+SP600125 group were significantly increased at different time points (P<0.05, P<0.01).</p><p><b>CONCLUSIONS</b>The vascular endothelial dysfunction under overfatigue conditions is related to the activity of the JNK/c-Jun/HO-1 pathway. One of the mechanisms of TXLSP in improving the vascular endothelial function is to adjust the activity of the JNK/c-Jun/HO-1 pathway at gene and protein levels.</p>

The endothelium injuries caused by homocysteine and treatmental effects of Tongxinluo powder / 中国应用生理学杂志

<p><b>AIM</b>To observe the effect of homocysteine (HCY) on the function of endothelium cell, and to discuss the possible mechanisms that Tongxinluo super powder affected.</p><p><b>METHODS</b>Healthy male Wistar rats were divided into randomly the control group, the model group, the Tongxinluo group. The effect of Ach on isolated rat thoracic aorta in vitro was examined, the microcirculation was observed by microcirculation meter, the activity of SOD and GSH-PX and content of NO, MDA, ET, Ang II, TXA2, PGI2 was detected.</p><p><b>RESULTS</b>Compared with control group, the effect of Ach on isolated rat thoracic aorta in vitro weakened markablely (P < 0.01), the format and percentage that capillary dilated declined significantly (P < 0.05), after treatment with Tongxinluo powder, the effect of Ach on isolated rat thoracic aorta in vitro was improved obviously (p < 0.01), and the format and percentage that capillary dilated were increased compared with model group; comparing with the control group, the level of Ang II and ET, TXA2 in plasm increased obviously (P < 0.05, P < 0.01), while the content of PGI2 depressed manifestly (P < 0.05), at the same time, both content of NO and activity of SOD, (GSH-PX declined obviously (P < 0.001, P < 0.05). After treatment with Tongxinluo powder, the level of ET, AngII and TXA2 reduced significantly in different degree (P < 0.01), while the content of PGI2 appeared stepping up notably (P < 0.01), and both activity of SOD and NO level increased obviously (P < 0.01, P < 0.05).</p><p><b>CONCLUSION</b>(1) The high homocystein might cause the contracted and dilated function decreased, it might get involved in endothelium disfunction as a result of the massive free radicals production and diastolic-contract factors balance disorder induced by high homocystein. (2) Tongxinluo powder could improve the function of endothelium-dependment dilation induced by high homocystein, that associated with inhibitting the excessive production of free radicals, and improved function of endothelium.</p>

Study on the regulatory effect of electro-acupuncture on hegu point (LI4) in cerebral response with functional magnetic resonance imaging / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study, through blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI), the cerebral activated areas evoked by electro-acupuncturing (EA) the right Hegu point (L14) or non-acupoint points on the face, and through comparing their similarities and differences, to speculate on the specific cerebral areas activated by stimulating L14, for exploring the mechanism of its effect in potential clinical application.</p><p><b>METHODS</b>EA was applied at volunteers' right L14 (of 9 subjects in the L14 group) and facial non-acupoint points (of 5 subjects in the control group), and whole brain 3-dimensional T1 anatomical imaging of high resolution 1 x 1 x 1 mm(3) used was performed with clustered stimulatory mode adopted by BOLD fMRI. Pretreatment and statistical t-test were conducted on the data by SPM2 software, then the statistical parameters were superimposed to the 3-dimensional anatomical imaging.</p><p><b>RESULTS</b>Data from 3 testees of the 9 subjects in the L14 group were given up eventually because they were unfit to the demand due to different causes such as movement of patients' location or machinery factors. Statistical analysis showed that signal activation or deactivation was found in multiple cerebral areas in 6 subjects of L14 group and 5 subjects of the control group (P<0.01). In the L14 group, the areas which showed signal activation were: midline nuclear group of thalamus, left supra marginal gyrus, left supra temporal gyrus, right precuneous lobe, bilateral temporal pole, left precentral gyrus and left cerebellum; those which showed signal deactivation were: bilateral hippocampus, parahippocampal gyrus, amygdala body area, rostral side/ audal side of cingulate gyrus, prefrontal lobe and occipital lobe as well as left infratemporal gyrus. In the control group, areas which showed signal activation were: bilateral frontal lobe, postcentral gyrus, Reil's island lobe, primary somato-sensory cortex, cingulate gyrus, superior temporal gyrus, occipital cuneiform gyrus and/or precuneus gyrus and right brainstem; and the area that showed deactivation was left median frontal lobe.</p><p><b>CONCLUSION</b>The effects of EA L14 in regulating cerebral activities could be displayed and recorded through BOLD fMRI, the distribution of signally deactivated area evoked by EA L14 was similar to the known distribution of anatomical orientation of pain in brain, and closely related to the anatomic structure of limbic system, which areas are possibly the acupuncture analgesic effect's cerebral regulating area. Furthermore, activated portion of left central anterior gyrus, which represent the movement of oral facial muscles, and the activated portion of cerebellum are possibly related with the effect of using EA L14 in treating facial palsy and facial muscle spasm. As for the mechanism of signal deactivation of cerebral activities exhibited in the present study that is unable to be elucidated, it awaits for further research.</p>