A Research Summary on the Chemical Constituents and Pharmacological Effects of the National Medicine Polygonum capitatum

Jingren CHEN Ao XIE Wei WEI Haicheng WEN

Abstract Polygonum capitatum Buch. Ham. ex D. Don is a commonly used medicine in Zhuang people's settlements， which has antipyretic， wind and evil-dispelling， dehumidifying and analgesic effects. The research on the chemical composition of P. capitatum began in the 1980s. Modern scientific research has shown that it has antibacterial， cooling and blood sugar lowering effect. In order to better develop and utilize P. capitatum， this paper reviewed the progress of the chemical composition and pharmacological research of P. capitatum.

Key words Polygonum capitatum; Touhualiao; Chemical composition; Pharmacological effects

Shimangcao refers to the whole plant of Polygonum capitatum Buch. Ham. ex D. Don， a perennial herbaceous plant. It is also known as Shilaliao， Touhualiao， Xiaohongliao， Taiyangcao， Mandihong， Sijihong and Huoliucao， and is named Rumdaengngonz in the Zhuang nationality. It tastes bitter， spicy， and is warm in nature. It has the effects of abating fever， dispelling wind， removing dampness and toxins， opening water channels， removing blood congestion， and relieving pain. In Zhuang medicine， it is mainly used to treat unnamed swelling， sore， diaper rash， yellow water sore， ulcer， rheumatism， eczema， gonorrhea， bruises and other diseases. It is distributed in Longlin， Tianlin， Lingyun， Nandan， Duan， Jinxiu， Gongcheng， Lingchuan and other counties and cities in Guangxi， as well as in Sichuan， Guizhou， Yunnan and other provinces in China[1]. Guangxi Traditional Chinese Medicine （Guangxi Zhongyaozhi） recorded its taste as "pungent， slightly astringent， warm in nature， dispelling and relieving pain， treating rheumatism and bruises". Yunnan Chinese Herbal Medicine （Yunnan Zhongcaoyao） called it Taiyangcao， and recorded "sour taste， cool in nature， clearing heat and diuretic， treating stranguria， hematuria and bladder inflammation". Wenshan Chinese Herbal Medicine （Wenshan Zhongcaoyao） called it as Mandihong and Hualiucao， which can treat rash and yellow water sore. It was recorded in the Medicine Standards of the Ministry of Health： Prescriptions of Traditional Chinese Medicine and entered the National Essential Drug List in 2000. At present， the patent medicines developed with P. capitatum as the main raw material include Relinqing Capsules and Relinqing Granules. The chemical composition and pharmacological effects of P. capitatum were reviewed as follows.

Chemical Composition Research

The research on the chemical composition of P. capitatum began in the 1980s， mainly from the aspects of the aboveground part， roots， phenolic acids， volatile oils， lignans， and triterpenes. Zhang[2] isolated 13 compounds from the aboveground part of P. capitatum， which were identified as 4-hydroxy-3，5-dimethoxybenzoic acid， catechol， 5，7-dihydroxy-4H-chromen-4-one， 3，5-dihydroxy-4-methoxybenzoic acid， ethyl protocatechuate， ethyl gallate， gallic acid， protocatechuic acid， quercetin， quercitrin， hirsutin （equercetin-3-O-β-D-glucopyranoside） and quercetin3-rhamnoside-2"-gallate. In 1985， Wu et al.[3] used ether and ethanol reflux extraction and silica gel column chromatography to obtain benzaldehyde， acetic acid， 24-hydroxytetracosanone-3，29-hydroxynonacosanone-3，β-sitosterol and gallic acid from P. capitatum for the first time. Li et al.[4] used 95% ethanol reflux extraction method to extract P. capitatum， and then performed silica gel and polyamide column chromatography to obtain quercetin， quercitrin， hirsutin （equercetin-3-O-β-D-glucopyranoside） and quercetin3-rhamnoside2"-gallate from P. capitatum for the first time. Mao et al.[5] used industrial ethanol reflux extraction and silica gel， macroporous resin and polyamide column chromatography to separate the flavonoid rutin from P. capitatum for the first time. Gao et al.[6] also isolated a new flavonoid from P. capitatum： 3′4′-methylenedioxy-3，5，6，7，8，5′-hexamethoxyflavone. Gao et al.[7] used steam distillation to extract the volatile components of P. capitatum， and used GC/MS for separation and determination. As a result， 88 compounds were separated and 51 were identified， mainly aldehydes， ketones， alcohols and terpenes， of which 1-octen-3-ol （1-octen-3-ol） showed the highest content， up to 15.205%. Ye et al.[8] applied silica gel column chromatography， reversed-phase ODS column chromatography， Sephadex LH-20 and other separation methods to separate and purify the hypoglycemic active components of P. capitatum， and a total of 7 lignans were isolated and identified as （+） isolariciresinol （1）， （-）-lyoniresinol-2a-O-[6-O-（4-hydroxy-3，5-dimethoxy） -benzoyl]-β-D-glucoside （2）， （-）-isolariciresinol -2a-O-β-D-xylopyranoside （3）， （+）-5′-methoxyisolariciresinol -9-O-β-D-xylopyranoside （4）， （-）-isolariciresinol-3a-O-β-D-glucoside （5）， nudiposide （6）， and lyoniside（7）. Among them， compounds 1， 2， 5， and 7 were isolated from this plant for the first time， compounds 2， 7 were isolated from a plant of the genus Polygonum for the first time， and compounds 1， 2， and 4 showed good in-vitro α-amylase inhibitory activity. Compound 2 had a significant inhibitory effect on α-amylase in vitro. The lignans in P. capitatum have hypoglycemic activity.

P. capitatum is rich in chemical components， and various compounds have been isolated and identified. However， the quality control standard of P. capitatum has not yet been formed， and it is still necessary to further explore the chemical composition of P. capitatum to provide quality control reference standards for the future development and utilization of P. capitatum.

Pharmacological Component Research

Drug metabolism

Sun et al.[9] combined UHPLC-Q-TOF/MS technology with Metabolite Tools TM， mass defect filter （MDF） and other metabolite analysis technologies to analyze the chemical solution of which each component had been exposed to the model organism zebrafish for 24 h and the metabolites in the model organism zebrafish， and found that gallic acid and protocatechuic acid mainly participated in methylation and sulfation reactions after acting with zebrafish. Sun et al.[10] studied the metabolism of the effective components of P. capitatum in rat feces and bile. A total of 4 prototype components and 26 metabolites were detected in rats. The feces and bile contained 12 and 19 components （including cross-components）， respectively， and the metabolites were mainly quercetin glucuronidation， methylglucuronidation， and sulfation metabolites. Xiang et al.[11] studied the serum medicinal chemistry of P. capitatum， and detected a large amount of glucuronidation， methylation and sulfation metabolites of the flavonoid quercetin in the drug-containing serum， as well as methylation and sulfation metabolites of phenolic acid components gallic acid， protocatechuic acid， etc. Tang et al.[12] carried out a study on the metabolism of the effective components of P. capitatum in vivo and in vitro. It was found that rats' serum， urine， feces and bile mainly contained the glucuronidation， methylglucuronidation and sulfation metabolites of quercetin.

P. capitatum exerts its main pharmacological effects with flavonoids and phenolic acids. The metabolic processes include quercetin glucuronidation， methylglucuronidation， and sulfation metabolism. In addition to flavonoids and phenolic acids， the drug metabolism mechanisms of other components of P. capitatum need further exploration.

Antimicrobial and anti-inflammatory effects

Zhao et al.[13] studied on the effects of P. capitatum on the structure and growth and metabolism of Helicobacter pylori. In 2016， Hu et al.[14] carried out a study on the material basis of the antibacterial effect of P. capitatum based on the spectrum-effect relationship. It was found that the antibacterial effect was the result of the combined action of multiple chemical components， and gallic acid， epicatechin， catechin， rutin， quercetin-3-O-（2″-O-galloyl）-β-D-glucopyranoside and quercetin were the main material basis for the antibacterial effect of P. capitatum. He et al.[15] studied the effects of P. capitatum on the outer membrane protein and genes omp8 and omp32 of H. pylori. P. capitatum up-regulated the outer membrane protein and omp8 and omp32 mRNA levels of H. pylori to cause changes in outer membrane permeability， thereby exerting antibacterial effects. Zhang et al.[16] studied the effects of P. capitatum on H. pylori urease activity and gene expression. P. capitatum inhibited H. pylori urease activity and down-regulated the expression levels of urease genes ure A and ure B to inhibit the synthesis of H. pylori urease， thereby reducing the survival ability of H. pylori in gastric acid environment. Feng et al.[17] carried out a study on the effects of P. capitatum on the levels of serum interferon-γ and interleukin-4 in rats with H. pylori gastritis. P. capitatum reduced the inflammatory damage of H. pylori to the gastric mucosa， and the mechanism might be realized by down-regulating the transcription level of IFN-γ mRNA. Zhang et al.[18] studied the effect of P. capitatum on the adhesion and colonization of H. pylori， and found that P. capitatum had a significant inhibitory effect on H. pylori. P. capitatum inhibited H. pylori urease activity， slowed down the flagellum power of H. pylori， and affected the adhesion of H. pylori to gastric mucosal epithelial cells， further exerting its antibacterial effect. Jian et al.[19] conducted a study on the effect of P. capitatum on the gastric mucosa and serum IL-17 and IL-23 expression levels in rats infected with H. pylori. Xu et al.[20] studied the anti-inflammatory substances of P. caputum and their mechanism of action. They found that the metabolism of gallic acid was the mainstay in the drug-containing serum， and the chemical constituents of P. capitatum might promote the release of certain endogenous molecules with anti-inflammatory effects in large quantities to achieve the efficacy. Jiang et al.[21] found that P. capitatum could improve the symptoms of gastritis caused by H. pylori by intervening in the TLRs pathway. Liu et al.[22] reported that the ethanol extract of P. capitatum had a better inhibitory effect on Staphylococcus aureus with multiple drug resistance than gallic acid， and P. capitatum also contained other antibacterial components besides gallic acid. Fang et al.[23] found that the water extract of P. capitatum inhibited the secretion of three inflammatory factors， NO， TNF-α， and PG2， and its inhibitory effect was concentration-dependent.

Blood sugar-lowering effect

Ye et al.[8]carried out a study on the sugar-reducing active ingredients of lignans in P. capitatum. Liu et al.[24]studied the effect of P. capitatum extract on the spontaneous model of type 2 diabetic db/db mice in 2017. Mei et al.[25]studied the hypoglycemic effect of three components in the effective components of P. capitatum in the model organism zebrafish. Chen et al.[26]showed that the methanol extract of P. capitatum had a very significant inhibitory effect on α-glucosidase activity.

Cooling effect

Ren et al.[27]studied the cooling effect of P. capitatum. The water extract of P. capitatum could not reduce the body temperature of normal rabbits， but it could reduce the pathological fever caused by typhoid and paratyphoid vaccines.

Acute toxicity

Liang et al.[28]studied Relinqing Granules， a traditional Chinese medicinal preparation refined from P. capitatum. They conducted acute toxicity tests on Relinqing Granules with mice and rats. The maximum tolerable dose of Relinqing Granules administered to mice was greater than 249.0 g/kg， and the maximum tolerable dose of Relinqing Granules administered to rats was greater than 124.5 g/kg. The values were 285.6 and 142.8 times the clinical doses， respectively. According to the results of acute toxicity test， the toxicity of the drug was relatively low.

It can be seen from the literature research of P. capitatum that the research on P. capitatum mainly focuses on the chemical components and the pharmacology of P. capitatum. The research involves many aspects， such as antibacterial effect， cooling effect， and acute toxicity. Especially， the research on P. capitatum should closely integrate the research of chemical composition and pharmacological mechanism. The above research results provide important reference for P. capitatum in quality control， clinical application and clinical medication guidance. However， the antibacterial effect of P. capitatum is mainly related to the resistance to peptic ulcers caused by H. pylori， and the research on infections caused by other Gram-positive bacteria is rarely involved. In addition， the cooling mechanism of P. capitatum has not been explored. Whether it triggers the central hypothalamic temperature sensor to achieve the cooling effect remains to be explored.

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