Weipixiao attenuate early angiogenesis in rats with gastric precancerous lesions

Zhao²,

BMC Complement Altern Med

et al. 2019

Self Cite

BackgroundAltered cellular metabolism is considered to be one of the hallmarks of cancer (Coller, Am J Pathol 184:4–17, 2014; Kim and Bae, Curr Opin Hematol 25:52–59, 2018). However, few studies have investigated the role of metabolism in the development of gastric precancerous lesions (GPLs). Weipiling (WPL), a traditional Chinese medicine formula for treatment of GPLs. In this study, we evaluated the amelioration of GPLs by WPL and investigated the possible role of WPL in regulating glucose metabolism.MethodsFirstly, the major components of WPL are chemically characterized by HPLC analytical method. In this study, we chose the Atp4a−/− mouse model (Spicer etal., J Biol Chem 275:21555–21565, 2000) for GPL analysis. Different doses of WPL were administered orally to mice for 10 weeks. Next, the pathological changes of gastric mucosa were assessed by the H&E staining and AB-PAS staining. In addition, TUNEL staining was used to evaluate apoptosis, and we further used immunohistochemically labelled CDX2, MUC2, ki-67, PTEN, and p53 proteins to assess the characteristic changes of gastric mucosa in precancerous lesions. The levels of such transporters as HK-II, PKM2, ENO1, MPC1, and LDHA were determined by Western blot analysis. Finally, we assessed the expression of mTOR, HIF-1α, AMPK, Rheb, TSC1 and TSC2 protein in the gastric mucosa of Atp4a−/−mice.ResultsIn this work, we evaluated the protective effect of WPL on gastric mucosa in mice with precancerous lesions. The aberrant apoptosis in gastric mucosa of gastric pre-cancerous lesions was controlled by WPL (P<0.05). Furthermore, WPL suppressed the expression of CDX2, MUC2, ki-67, PTEN and p53, as the levels of these proteins decreased significantly compared with the model group (P<0.05). In parallel, WPL significantly suppressed the expression of transporters, such as HK-II, PKM2, ENO1, MPC1 and LDHA (P<0.05). In addition, mTOR, HIF-1a, AMPK, Rheb, TSC1 and TSC2 protein levels in gastric mucosa of Atp4a−/− mice in the high- and low-dose WPL groups were significantly lower than those in the model group (P<0.05), while the expression of TSC1 and TSC2 protein was significantly higher (P<0.05).ConclusionsConclusively, WPL could ameliorate GPLs in Atp4a−/− mice by inhibiting the expression of transporters and suppressing the aberrant activation of mTOR/HIF-1α.

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Weipiling ameliorates gastric precancerous lesions in Atp4a−/− mice

Zhao²,

BMC Complement Altern Med

et al. 2019

Self Cite

“…Blood activating and stasis removing (BASR) is the main principle in traditional Chinese medicine for treatment of cardiovascular diseases. Previous studies have reported that BASR-CHMs promote angiogenesis by upregulating vascular endothelial growth factor (VEGF) gene in the ischemic model (Xin et al, 2018; Zheng et al, 2018; Shi et al, 2019) and inhibit angiogenesis mainly by downregulating VEGF and decreasing MMP9 expression in tumor tissues (Zeng et al, 2018). There are also reports in the literature of the side effect caused by BASRs in abnormally promoting normal blood vessel growth (Su et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Untargeted Safety Pharmacology Screen of Blood-Activating and Stasis-Removing Patent Chinese Herbal Medicines Identified Nonherbal Ingredients as a Cause of Organ Damage in Experimental Models

Shao

Yang

et al. 2019

Front. Pharmacol.

Blood activation and stasis removal from circulation is a central principle for treatment of syndromes related to cerebral and cardiovascular diseases in Chinese herbal medicine. However, blood-activating and stasis-removing patent Chinese herbal medicine (BASR-pCHM) widely used with or without prescription in China and elsewhere are highly variable in composition and manufacture standard, making their safety assessment a challenging task. We proposed that an integrated evaluation of multiple toxicity parameters of BASR-pCHM would provide critical reference and guidelines for their safe clinical application. Examination of standardized extracts from 58 compound BASR-pCHM in vivo in VEGFR2-luc mice and in vitro in cardiac, renal, and hepatic cells identified Naoluotong capsule (NLTC) as a potent organ/cell damage inducer. Composition analysis revealed that NLTC was the one that contained nonherbal ingredients among the BASR-pCHM collection. In vivo and in vitro experiments confirmed that NLTC, as well as its chemical supplement tolperisone hydrochloride, caused organ and cell damage by reducing cell viability, mitochondrial mass/activity, while the NLTC herbal components did not. Taken together, our study showed that safety evaluation of patent herbal medicines already on market is still necessary and urgently needed. In addition, chemical/herbal interactions should be considered as an important contributor of potential toxicity when evaluating the safety of herbal medicine.

Evidence-Based Complementary and Alternative Medicine

“…e use of herbal medicine within this system has been viewed as an effective measure to prevent chronic diseases. It has been proven that the use of TCM is effective in blocking and reversing majority of GPL developments [16][17][18]. As shown in Figure 1, this paper elucidates forms of TCM treatment for the prevention and treatment of GPL, including herbal formulations and TCM active ingredients.…”

Section: Introductionmentioning

confidence: 95%

“…Activated HIF-1α in tumor cells can increase the expression and activity of glycolytic enzymes, including GLUT1 and HK2, to accelerate the glycolytic rate [103]. Chinese medicine prescriptions such as Weipixiao formula and Weiqi decoction have been proven to attenuate GPL by suppressing levels of HIF-1α [16,39], suggesting their potential antiglycolytic function.…”

Section: Inhibition Of Glycolysis Aerobic Glycolysis or Thementioning

confidence: 99%

“…Another study indicated that its pharmacological mechanisms might be associated with modulation of the VEGF signaling pathway [111]. Experiments on rats with GPL verified that Weipixiao could attenuate early angiogenesis with a concomitant regression of precancerous lesions by suppressing VEGF activation [16]. e Weining granules, a Chinese prescription composed of Radix Astragali, Poria cocos, Rhizoma Curcumae Longae, and Fructus Lycii, has been applied in the integrative treatment of patients with GPL.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Systematic Review of the Mechanisms Underlying Treatment of Gastric Precancerous Lesions by Traditional Chinese Medicine

Fan

et al. 2020

Self Cite

Gastric precancerous lesions (GPLs) are an essential precursor in the occurrence and development of gastric cancer, known to be one of the most common and lethal cancers worldwide. Traditional Chinese medicine (TCM) has a positive prospect for the prevention and therapy of GPL owing to several advantages including a definite curative effect, fewer side effects compared to other treatments, multiple components, and holistic regulation. Despite these characteristic advantages, the mechanisms of TCM in treating GPL have not been fully elucidated. In this review, we summarize the current knowledge with respect to herbal formulations and the therapeutic mechanisms of TCM active ingredients for GPL. This paper elaborates on the mechanisms of TCM underlying the prevention and treatment of GPL, specifically those that are linked to anti-H. pylori, anti-inflammation, antiproliferation, proapoptotic, antioxidation, antiglycolytic, and antiangiogenesis effects.