Pharmacological Effects And Clinical Applications Of Polygonum Capitatum

2 Pharmacological Activities

2.1 Antioxidant Activity

Oxidative stress can lead to lipid membrane peroxidation, compromising membrane integrity, causing cell death, and contributing to severe diseases such as atherosclerosis, stroke, diabetes, Alzheimer's disease, and cancer. Studies have shown that flavonoids and phenolic acids in Polygonum capitatum extracts are the primary components responsible for its antioxidant activity [12].

Liu Zhijun et al. [16] isolated and purified 10 compounds from the whole herb of Polygonum capitatum using polyamide, Sephadex LH-20, and silica gel column chromatography. These compounds were identified as flavonoids and phenolic acids. The antioxidant capacity of six monomeric compounds (gallic acid, protocatechuic acid, gallic acid ethyl ester, kaempferol, quercetin, and quercitrin) in scavenging three reactive oxygen species (O₂⁻, OH, and H₂O₂) was evaluated using three systems:

The o-phenanthroline-Cu²⁺-ascorbic acid-H₂O₂ system,

The H₂O₂-luminol-carbonate buffer system (pH 9.5),

The pyrogallol-luminol-carbonate buffer system (pH 10.2).

The results demonstrated that all six compounds exhibited scavenging effects on the three reactive oxygen species, though their effectiveness varied. For example, quercitrin and kaempferol were more effective in scavenging H₂O₂ than the other compounds. All six compounds contained ortho-diphenol hydroxyl groups, suggesting that the ortho-diphenol hydroxyl structure is closely associated with their antioxidant activity and may significantly influence it.

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Yan Xinglian et al. [29] used petroleum ether, methanol, and ethyl acetate to extract Polygonum capitatum and assessed its antioxidant activity by measuring:

The scavenging of ABTS free radicals [(2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt],

The scavenging of DPPH free radicals [(1,1-diphenyl-2-picryl-hydrazyl)],

The ferric-reducing antioxidant power (FRAP).

The methanol extract exhibited the strongest free radical scavenging and Fe³⁺-reducing capacities, with its total antioxidant capacity far exceeding that of positive controls BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole). The results indicated that the antioxidant activity of Polygonum capitatum is related to the polarity of the extraction solvent, with higher solvent polarity enhancing antioxidant capacity.

Yun Chengyue et al. [30] similarly extracted Polygonum capitatum using solvents of varying polarity (petroleum ether, chloroform, ethyl acetate, n-butanol, and water). The ethyl acetate extract showed the strongest antioxidant capacity, while the water extract exhibited the weakest. These findings align with those of Yan Xinglian et al. [29], confirming that the antioxidant activity of Polygonum capitatum is influenced by the extraction solvent, with solvent polarity playing a critical role.

Gong Jinyan et al. [31] studied the effect of ethanol precipitation on the antioxidant activity of the water extract of Polygonum capitatum. By measuring the scavenging ability of ABTS and DPPH free radicals, they concluded that ethanol precipitation significantly enhanced the antioxidant activity of the water extract.

In summary, current research indicates that the antioxidant activity of Polygonum capitatum is related to the polarity of the extraction solvent (as it affects the polarity of extracted compounds) and the ortho-diphenol hydroxyl structure in its compounds. Methods such as ethanol precipitation can further improve its antioxidant activity. However, more research is needed on the antioxidant activity of individual components in Polygonum capitatum.

 

2.2 Anti-Inflammatory Activity

Inflammation is involved in numerous complex diseases and disorders, including autoimmune diseases, metabolic syndromes, neurodegenerative diseases, cancer, and cardiovascular diseases. Studies have demonstrated that Polygonum capitatum extracts possess anti-inflammatory activity. The primary mechanisms identified in existing research include inhibiting the release of inflammatory factors via the nuclear factor-κB (NF-κB) pathway, regulating the levels of p38MAPK, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) genes, and affecting the phosphorylation of inhibitor kappa B alpha (IκBα), NF-κB p65, p38MAPK, and ERK1/2, as well as the nuclear translocation of NF-κB p65 and p-p38MAPK.

For example, Xu Dan [32], using pharmacological and pharmacochemical methods, established an inflammatory damage model in mouse mononuclear macrophage RAW264.7 cells induced by lipopolysaccharide (LPS). The anti-inflammatory activity of different Polygonum capitatum water extract serum preparations was evaluated based on the release of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α). These preparations included:

PCAWES (serum containing the ethanol-precipitated water extract of Polygonum capitatum),

PCAPWES (serum containing the ethanol-precipitated precipitate of the water extract), and

PCWES (serum containing the water extract).

All serum preparations inhibited the release of inflammatory factors to varying degrees. The PCAWES group exhibited the strongest anti-inflammatory activity, significantly inhibiting the release of NO, TNF-α, and interleukin-6 (IL-6). The mechanism was shown to involve suppression of NO, TNF-α, and IL-6 release, reduction of iNOS, TNF-α, and IL-6 mRNA levels, and decreased expression of p-IκBα protein in the NF-κB signaling pathway. However, there was no significant impact on the p-p38 protein expression in the MAPK pathway. The active components in the serum responsible for the anti-inflammatory effects were primarily endogenous molecules, and the specific anti-inflammatory components in Polygonum capitatum remain to be identified.

Zhang et al. [33] studied the effects of quercetin, a component of Polygonum capitatum, on Helicobacter pylori-related gastric inflammation. Using a mouse model of H. pylori infection, the experimental mice were divided into three groups:

Control group (healthy mice, CG),

Model group (H. pylori-infected mice, MG),

Quercetin group (quercetin-treated H. pylori-infected mice, QG).

The results showed that quercetin treatment in the QG group reduced the levels of p38MAPK and Bax while increasing Bcl-2 levels (P < 0.05). This regulation of the balance between gastric cell proliferation and apoptosis helped prevent gastritis. The findings indicate that quercetin in Polygonum capitatum may prevent H. pylori-related gastric inflammation and apoptosis by modulating the levels of p38MAPK, Bcl-2, and Bax genes.

Meanwhile, Song et al. [34] employed network pharmacology to predict the mechanisms by which Polygonum capitatum affects Helicobacter pylori-related gastritis (HAG). The study showed that Polygonum capitatum exerts its effects by influencing the phosphorylation of IκBα, NF-κB p65, p38MAPK, and ERK1/2, as well as the nuclear translocation of NF-κB p65 and p-p38MAPK. These findings were validated through in vivo and in vitro experiments, demonstrating that Polygonum capitatum may act on multiple targets and pathways, playing a key role in the treatment of HAG.

2.3 Antibacterial Activity

Polygonum capitatum exhibits broad antibacterial activity, effectively inhibiting and killing various bacteria and fungi, including Staphylococcus aureus, Helicobacter pylori (Hp), Escherichia coli, Neisseria gonorrhoeae, Klebsiella pneumoniae, and Proteus mirabilis.

Liao et al. [35] conducted antibacterial tests on extracts and components of Polygonum capitatum. The results revealed that tannins and flavonoids in Polygonum capitatum effectively inhibited the growth of E. coli, K. pneumoniae, and S. aureus. Yun Chengyue et al. [36] found that Polygonum capitatum exhibited notable antibacterial activity, with good inhibitory effects on S. aureus and E. coli at a concentration of 20 mg/mL.

Some researchers have also studied the antibacterial activity of individual components in Polygonum capitatum. Zhang Liyan et al. [37] used the drug sensitivity disk diffusion method to investigate the active components responsible for anti-Neisseria gonorrhoeae activity in Polygonum capitatum extracts. Results indicated that tri-galloyl-glucose might be the primary antibacterial substance. Liu Yuxin et al. [38], using disk diffusion and microdilution methods, discovered that in addition to gallic acid, other antibacterial components are present in Polygonum capitatum extracts.

Further studies have explored the antibacterial mechanisms of Polygonum capitatum. Zhang Shu et al. [39] investigated its anti-H. pylori mechanism, using two-dimensional gel electrophoresis and real-time PCR to evaluate the effects of Polygonum capitatum on H. pylori protein and gene expression. Results showed that the expression levels of KatA, TsaA, and TagD genes in the experimental group were significantly downregulated by 1.52, 2.94, and 3.65 times, respectively, compared to the control group. This indicates that the antibacterial mechanism of Polygonum capitatum against H. pylori involves impairing its antioxidant system, reducing its survival capacity in vitro, and potentially serving as a key therapeutic target to decrease the pathogenicity of H. pylori.

2.4 Antidiabetic Activity

Research has shown that lignans and flavonoids in Polygonum capitatum are the primary constituents responsible for its antidiabetic effects. The mechanism is related to the regulation of peroxisome proliferator-activated receptor-alpha (PPAR-α), glucose transporter type 4 (GLUT4), and 5-AMP activated protein kinase (AMPK) gene expression.

Tong Nansen et al. [40] studied the antidiabetic mechanism of Polygonum capitatum using human liver cancer HepG2 cells. The extract significantly promoted glucose uptake by HepG2 cells and upregulated PPAR-α and GLUT4 gene expression, as well as inhibiting α-glucosidase activity.

Li Yaya et al. [41] conducted in vitro and in vivo studies on the antidiabetic mechanism of Polygonum capitatum. Using HepG2 cells and db/db type 2 diabetic mice as models, their results indicated that the extract significantly promoted glucose uptake in HepG2 cells and upregulated PPAR-α and GLUT4 gene expression. In vivo, the extract reduced body weight, blood glucose levels, and improved glucose tolerance in db/db mice. It also increased the expression of AMPK and GLUT4 in the liver. Further analysis identified myricetin, kaempferol, and quercetin as the active compounds, which achieve antidiabetic effects through α-glucosidase inhibition. Additionally, lignans such as (+)-isolariciresinol, (−)-arctigenin, and (+)-5'-methoxy-isolariciresinol-9-O-β-D-xylopyranoside in Polygonum capitatum were confirmed to exhibit significant antidiabetic activity [23]. Polygonum capitatum was also found to improve insulin resistance in db/db mice, enhancing glucose uptake in liver tissues by upregulating AMPK and GLUT4 gene expression [42].

 

2.5 Antipyretic and Analgesic Activity

Polygonum capitatum exhibits notable antipyretic and analgesic effects. Studies on rabbits showed that its water extract reduced fevers induced by intravenous injection of Salmonella typhi and Salmonella paratyphi. Analgesic tests on mice revealed that both water and ethanol extracts of Polygonum capitatum produced significant pain relief [43-44].

 

2.6 Lipid-Lowering Activity

The lipid-lowering mechanism of Polygonum capitatum primarily involves its effects on the human phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/NF-κB signaling pathway. Studies have shown that flavonoids in Polygonum capitatum improve blood lipid levels in high-fat and atherosclerotic rat models, while protecting the liver. In atherosclerotic rats, Polygonum capitatum reduced blood lipid levels, inflammatory factors, blood viscosity, hematocrit, and vascular active factor levels. It also decreased the levels of PI3K-p110, PI3K-p85, Akt, and NF-κB-p65 in the aortic tissue [45].

 

2.7 Anticancer Activity

Research has shown that Polygonum capitatum extracts and active components, such as Davidin, exhibit significant efficacy in inhibiting the proliferation of liver cancer cells. For example, studies by Hooper and Neish et al. [46-47] revealed that ethanol extracts of Polygonum capitatum and components like Davidin exhibit inhibitory effects on the proliferation of liver cancer cells. Additionally, He Chiyu et al. [48] identified the compound FR429 from Polygonum capitatum extracts, which was found to suppress the growth of liver cancer cells, suggesting that Polygonum capitatum extracts may possess anticancer activity.

 

3 Clinical Applications

3.1 Traditional and Ethnic Uses of Polygonum capitatum

As a characteristic herbal medicine of Guizhou Province, Polygonum capitatum is known in Miao medicine as "Dlob dongd xok" and has been widely used in traditional and ethnic medicine for centuries. Traditional medicine records describe its applications in treating urinary tract infections, urinary stones, traumatic injuries, pyelonephritis, dysentery, hematuria, cystitis, rheumatism, diaper rash, impetigo, sores, and ascariasis.

For instance:

The Quality Standards for Chinese and Ethnic Medicinal Materials of Guizhou Province describes it as having a bitter, pungent taste and a cooling nature. It is associated with the kidney and bladder meridians and is used to treat dysentery, cystitis, pyelonephritis, prostatitis, urinary stones, pelvic inflammation, rheumatic pain, traumatic injuries, and eczema.

The Chinese Medicinal Herbs of Yunnan records its primary functions as clearing heat, promoting diuresis, and relieving stranguria.

The Guangxi Medicinal Records describes its use for dispelling wind-dampness and relieving pain caused by blood stasis.

The Research and Development of Miao Medicine in Guizhou highlights its use for cystitis, nephritis, urinary stones, traumatic injuries, and as a diuretic for relieving stranguria.

In addition, Polygonum capitatum is often used either alone or in combination with other Chinese herbs to treat various diseases. Its combinations and usage are detailed in Table 5.

 

 

Summary

Polygonum capitatum, a traditional herb widely used in ethnic medicine, exhibits diverse pharmacological effects, including antioxidant, anti-inflammatory, antibacterial, antidiabetic, antipyretic, analgesic, lipid-lowering, and anticancer activities. Its active compounds, such as flavonoids, lignans, tannins, and Davidin, contribute to these effects through mechanisms like regulating signaling pathways (e.g., NF-κB, MAPKs, PPAR-α) and inhibiting harmful factors. Clinically, it has been traditionally used for treating urinary tract infections, kidney inflammation, dysentery, rheumatism, and traumatic injuries, reflecting its importance in both modern research and traditional practices.