## 4 Therapeutic Potential of Plant Extracts and Phytochemicals
### Extracts and Bioactive Components of Polygonum multiflorum  
Polygonum multiflorum (PM), also named _Pleuropterus multiforus_, _Fallopia multiflora_, or _Reynoutria multiflora_, is the most widely used plant in the treatment of hair graying. This plant has been used in traditional medicine to treat various disorders [132]. It has two different medicinal forms, _Polygonum multiflorum_ Radix (PMR) and _Polygonum multiflorum_ Radix Preparata (PMRP), a processed form prepared by steaming PMR with black soybean decoction [133; 134]. The main phytochemical components of PM can be classified into stilbenes, quinones, flavonoids, and others, as described in comprehensive reviews of this plant [135; 136]. In high-performance liquid chromatography (HPLC) analysis, 2,3,5,4\({}^{\prime}\)-tetrahydrooxystilbene-2-O-\(\beta\)-D-glucose (TSG), emodin, emodin-8-O-\(\beta\)-D-glucopyranoside, physcon, and torachrysone-8-O-\(\beta\)-D-glucose appeared as the major peaks [137; 138]. Of these, TSG has been most extensively studied as the main active compound responsible for the pharmacological activities of PM [139; 140]. Table 1 shows the biological activities of PM extracts and their phytochemical components evaluated in various experimental models to study melanin synthesis or hair pigmentation. \begin{table}
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**Models** & **Plant Extracts or** & **Treatments** & **Efficacy** & **Molecular Targets** & **Reference** \\ \hline Six-week-old CS7 BL/6 male mice (10 animals per group); back rats attached with 0.0375\% & PMR extract, PMRP extract, and TSG extract, and TSG extract (0.576 kg\({}^{-1}\)) & PMR extract, PMRP, and TSG and topical & PMR extract, PMRP extract, and TSG reversed the total median content of hairs attached by H2O2. & PMR extract, PMRP extract, and TSG reversed the expression median content of hairs attached by H2O2. & PMR extract presented the expression median content of hairs attached by H2O2. & PMR extract presented the expression median content of hairs attached by H2O2. & TSG reversed the expression levels of a-MSH, MCIR, and TYR downregulated by H2O2. \\ H2O2 solution & & & & \\  & & & & \\  & & & & \\  
The hair-blackening effects of PMR extract, PMRP extract, and TSG in pure form were examined in 6-week-old C57 BL/6J male mice (10 animals per group) with H2O2-induced hair bleaching [134]. For the model group, the 0.0375% H2O2 solution was spread on their back furs every morning for 6 weeks. Six hours after each H2O2 treatment, mice fasted for 2 h and received PMR extract (0.576 g kg\({}^{-1}\) by gavage and 1.152 g kg\({}^{-1}\) topically), PMRP extract (0.576 g kg\({}^{-1}\) by gavage and 1.152 g kg \({}^{-1}\) topically), or TSG (0.034 g kg\({}^{-1}\) by gavage and 0.068 g kg\({}^{-1}\) topically). The total melanin content of hairs was lowered by H2O2, which was reversed by PMR and PMRP extracts. When the expression of POMC, \(\alpha\)-MSH, MC1R, agouti signaling protein (ASIP), MITF, TYR, TYRP1, and TYRP2 in the skin was analyzed by enzyme-linked immunosorbent assay (ELISA), only \(\alpha\)-MSH, MC1R, and TYR levels were significantly downregulated by H2O2 and reversed by the PMRP extract, PMRP extract, or TSG in the order of activity. [PERSON] et al. reported the effects of PMR and PMRP extracts in protecting melanocytes from oxidative stress [141]. The water extract of PMRP reduced the intracellular ROS levels at 0.05, 0.1, 0.2, or 0.5 ug mL\({}^{-1}\) while preserving the intracellular level of GSH at 0.05 ug mL\({}^{-1}\) in primary human foreskin melanocytes exposed to 250 uM H2O2. PMR extract (0.01 mg mL\({}^{-1}\)) prevented cell death induced by 1100\(-\)1750 uM H2O2. PMR extract (0.1 mg mL\({}^{-1}\)) also enhanced pigmentation in human hair follicles ex vivo.