Compendium of the most significant studies with reference to properties, intake, effects.

Kim MJ, Kang HH, Seo YJ, Kim KM, Kim YJ, Jung SK. Paeonia lactiflora Root Extract and Its Components Reduce Biomarkers of Early Atherosclerosis via Anti-Inflammatory and Antioxidant Effects In Vitro and In Vivo. Antioxidants (Basel). 2021 Sep 23;10(10):1507. doi: 10.3390/antiox10101507. 

Abstract. Although various physiological activities of compounds obtained from Paeonia lactiflora have been reported, the effects of P. lactiflora extract (PLE) on early atherosclerosis remain unclear. Therefore, in this study, we investigated the in vitro and in vivo antiatherosclerosis and in vitro antioxidant effects of PLE and its compounds. PLE suppresses the tumor necrosis factor (TNF)-α-induced capacity of THP-1 cells to adhere to human umbilical vein endothelial cells (HUVECs), vascular cell adhesion molecule (VCAM)-1 expression, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in HUVECs. PLE also suppresses TNF-α-induced nuclear translocation of NF-κB p65 from cytosol as well as the enhanced TNFA and C-C motif chemokine ligand 2 (CCL2) mRNA expression in HUVECs. We identified and quantified the following PLE compounds using high-performance liquid chromatography with diode array detection: methyl gallate, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, benzoic acid, benzoylpaeoniflorin, and paeonol. Among these, methyl gallate had the strongest inhibitory effect on monocyte adherence to TNF-α-induced HUVECs and the VCAM-1 expression. Reverse transcriptase real-time quantitative polymerase chain reaction showed that PLE compounds had a dissimilar inhibition effect on TNF-α-induced mRNA expression levels of CCL2, TNFA, and IL6 in HUVECs. Except for paeonol, the compounds inhibited lipopolysaccharide (LPS)-induced reactive oxygen species production in RAW264.7 cells. In vivo, oral administration of PLE improved TNF-α-induced macrophage infiltration to the vascular endothelium and expression of VCAM-1, as well as IL6 and TNFA gene expression in the main artery of mice. PLE could be useful as a nutraceutical material against early atherosclerosis via the combined effects of its components.

Yoshie Y, Ando H, Tamura T, Fukuda K, Igarashi M, Hishida A, Kawahara N, Sasaki Y. Development of SCAR Markers to Identify Medicinal Cultivars of Paeonia lactiflora. Biol Pharm Bull. 2022;45(3):292-300. doi: 10.1248/bpb.b21-00810. 

Abstract. Paeoniae Radix, the dried root of Paeonia lactiflora, is one of the most important ingredients in Kampo medicine. It is known that Paeoniae Radix is derived from various P. lactiflora cultivars, including medicinal and horticultural cultivars, and that cultivar identification by DNA analysis has been unsuccessful. We attempted to develop sequence characterized amplified region (SCAR) markers as useful DNA markers for the identification and herbal medicine authentication of two cultivars developed in Japan, 'Bonten' and 'Kitasaisho,' which are two superior medicinal strains of P. lactiflora. Sequence-related amplified polymorphism (SRAP) analysis was conducted on fourteen P. lactiflora cultivars, and polymorphic fragments specific to 'Bonten' or 'Kitasaisho' were detected. Then, SCAR markers for 'Bonten' and 'Kitasaisho' were developed from the sequence information of these polymorphic fragments. Thirty cultivars of P. lactiflora and five herbal medicine samples were used to validate the specificity of the developed SCAR markers. As a result, we confirmed that our SCAR markers can identify 'Bonten' or 'Kitasaisho' from the plant samples and the herbal medicine samples. Thus, we have successfully designed two highly specific DNA markers and established an easy, rapid, and cost-efficient method to identify specific cultivars of P. lactiflora. Our SCAR markers are expected to contribute to the maintenance of P. lactiflora cultivars such as 'Bonten' as superior medicinal strains, the development of more elite cultivars in the future, and the deterrence of outflow of original cultivars to foreign countries.

Zhang L, Wei W. Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony. Pharmacol Ther. 2020 Mar;207:107452. doi: 10.1016/j.pharmthera.2019.107452. 

Abstract. As a Traditional Chinese Medicine, Paeonia lactiflora Pallas has been used to treat pain, inflammation and immune disorders for more than 1000 years in China. Total glycoside of paeony (TGP) is extracted from the dried root of Paeonia lactiflora Pallas. Paeoniflorin (Pae) is the major active component of TGP. Our research group has done a lot of work in the pharmacological mechanisms of Pae and found that Pae possessed extensive anti-inflammatory and immune regulatory effects. Pae could inhibit inflammation in the animal models of autoimmune diseases, such as experimental arthritis, psoriatic mice and experimental autoimmune encephalomyelitis, and so on. Pae modulates the functions and activation of immune cells, decreases inflammatory medium production, and restores abnormal signal pathway. Pae could balance the subsets of immune cells through inhibiting abnormal activated cell subsets and restoring regulatory cell subsets. Pae could regulate signaling pathways (GPCR pathway, MAPKs /NF-κB patway, PI3K /Akt /mTOR pathway, JAK2 /STAT3 pathway, TGFβ /Smads, and etc.). TGP is composed of Pae, hydroxyl-paeoniflorin, paeonin, albiflorin and benzoylpaeoniflorin etc. Pae accounts for more than 40% of TGP. Like Pae, TGP has anti-inflammatory and immune regulatory effects. TGP has been widely used to treat autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, allergic contact dermatitis, and etc. in China. Furthermore, TGP has some superior features with immune regulation, gentle effect, many indications and few adverse drug reactions. These findings suggest that TGP may be a promising anti-inflammatory and immune drug with soft regulation and has more superiority in the treatment of AIDs. Currently, TGP is used for the treatment of RA, SLE and other AIDs in more than 1000 hospitals in China, which obtained great social and economic benefits. Copyright © 2019 The Authors. 

Zhang T, Cao S, Yuan H, Park S. Alleviation of Androgenetic Alopecia with Aqueous Paeonia lactiflora and Poria cocos Extract Intake through Suppressing the Steroid Hormone and Inflammatory Pathway. Pharmaceuticals (Basel). 2021 Nov 5;14(11):1128. doi: 10.3390/ph14111128. 

Abstract. Paeonia lactiflora Pallas (PL) and Poria cocos Wolf (PC) have been traditionally used to treat inflammatory diseases reported in Dongui Bogam and Shen Nong Ben Cao Jing, traditional medical books in Korean and China, respectively. We determined the efficacies and the molecular mechanisms of PL, PC, and PL + PC aqueous extracts on androgenetic alopecia (AGA) induced by testosterone propionate in C57BL/6 mice. The molecular mechanisms of PL and PC in AGA treatment were examined using experimental assays and network pharmacology. The AGA model was generated by topically applying 0.5% testosterone propionate in 70% ethanol solution to the backs of mice daily for 28 days while the normal-control (Normal-Con; no AGA induction) mice applied 70% ethanol. The 0.1% PL (AGA-PL), 0.1% PC (AGA-PC), 0.05% PL + 0.05% PC (AGA-MIX), and 0.1% cellulose (AGA-Con; control) were supplemented in a high-fat diet for 28 days in AGA-induced mice. Positive-control (AGA-Positive) were administered 2% finasteride daily on the backs of the AGA mice. Hair growth rates decreased in the order of AGA-PL, AGA-MIX, AGA-PC, AGA-Positive, and AGA-Con after 21 days of treatment (ED21). On ED28, skins were completely covered with hair in the AGA-PL and AGA-MIX groups. Serum testosterone concentrations were lower in the AGA-PL group than in the AGA-Con group and similar to concentrations in the Normal-Con group, whereas serum 17β-estradiol concentrations showed the opposite pattern with increasing aromatase mRNA expression (p < 0.05). In the dorsal skin, DKK1 and NR3C2 mRNA expressions were significantly lower, but TGF-β2, β-Catenin, and PPARG expressions were higher in the AGA-PL and AGA-PC groups than in the AGA-Con group (p < 0.05), whereas TNF-α and IL-6 mRNA expressions were lower in the AGA-PL, AGA-MIX, and Normal-Con groups than in the AGA-Con group (p < 0.05). The phosphorylation of Akt and GSK-3β in the dorsal skin was lower in AGA-Con than normal-Con, and PL and MIX ingestion suppressed their decrease similar to the Normal-Con. In conclusion, PL or PL + PC intake had beneficial effects on hair growth similar to Normal-Con. The promotion was related to lower serum testosterone concentrations and pro-inflammatory cytokine levels, and inhibition of the steroid hormone pathway, consistent with network pharmacology analysis findings.

Lee HS, Kim Y. Paeonia lactiflora Inhibits Cell Wall Synthesis and Triggers Membrane Depolarization in Candida albicans. J Microbiol Biotechnol. 2017 Feb 28;27(2):395-404. doi: 10.4014/jmb.1611.11064. 

Abstract. Fungal cell walls and cell membranes are the main targets of antifungals. In this study, we report on the antifungal activity of an ethanol extract from Paeonia lactiflora against Candida albicans, showing that the antifungal activity is associated with the synergistic actions of preventing cell wall synthesis, enabling membrane depolarization, and compromising permeability. First, it was shown that the ethanol extract from P. lactiflora was involved in damaging the integrity of cell walls in C. albicans. In isotonic media, cell bursts of C. albicans by the P. lactiflora ethanol extract could be restored, and the minimum inhibitory concentration (MIC) of the P. lactiflora ethanol extract against C. albicans cells increased 4-fold. In addition, synthesis of (1,3)-β-D-glucan polymer was inhibited by 87% and 83% following treatment of C. albicans microsomes with the P. lactiflora ethanol extract at their 1× MIC and 2× MIC, respectively. Second, the ethanol extract from P. lactiflora influenced the function of C. albicans cell membranes. C. albicans cells treated with the P. lactiflora ethanol extract formed red aggregates by staining with a membrane-impermeable dye, propidium iodide. Membrane depolarization manifested as increased fluorescence intensity by staining P. lactiflora-treated C. albicans cells with a membrane-potential marker, DiBAC4(3) ((bis-1,3-dibutylbarbituric acid) trimethine oxonol). Membrane permeability was assessed by crystal violet assay, and C. albicans cells treated with the P. lactiflora ethanol extract exhibited significant uptake of crystal violet in a concentration-dependent manner. The findings suggest that P. lactiflora ethanol extract is a viable and effective candidate for the development of new antifungal agents to treat Candida-associated diseases.

Ko CY, Chao J, Chen PY, Su SY, Maeda T, Lin CY, Chiang HC, Huang SS. Ethnobotanical Survey on Skin Whitening Prescriptions of Traditional Chinese Medicine in Taiwan. Front Pharmacol. 2021 Nov 30;12:736370. doi: 10.3389/fphar.2021.736370. 

Abstract. The increasing interest and demand for skin whitening products globally, particularly in Asia, have necessitated rapid advances in research on skin whitening products used in traditional Chinese medicine (TCM). Herein, we investigated 74 skin whitening prescriptions sold in TCM pharmacies in Taiwan. Commonly used medicinal materials were defined as those with a relative frequency of citation (RFC) > 0.2 and their characteristics were evaluated. Correlation analysis of commonly used medicinal materials was carried out to identify the core component of the medicinal materials. Of the purchased 74 skin whitening prescriptions, 36 were oral prescriptions, 37 were external prescriptions, and one prescription could be used as an oral or external prescription. After analysis, 90 traditional Chinese medicinal materials were obtained. The Apiaceae (10%; 13%) and Leguminosae (9%; 11%) were the main sources of oral and external medicinal materials, respectively. Oral skin whitening prescriptions were found to be mostly warm (46%) and sweet (53%), while external skin whitening prescriptions included cold (43%) and bitter (29%) medicinal materials. Additionally, mainly tonifying and replenishing effects of the materials were noted. Pharmacological analysis indicated that these medicinal materials may promote wound healing, treat inflammatory skin diseases, or anti-hyperpigmentation. According to the Spearman correlation analysis on interactions among medicinal materials with an RFC > 0.2 in the oral skin whitening prescriptions, Paeonia lactiflora Pall. (white) and Atractylodes macrocephala Koidz. showed the highest correlation (confidence score = 0.93), followed by Ziziphus jujuba Mill. (red) and Astragalus propinquus Schischkin (confidence score = 0.91). Seven medicinal materials in external skin whitening prescriptions with an RFC > 0.2, were classified as Taiwan qī bái sàn (an herbal preparation), including Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav., Wolfiporia extensa (Peck) Ginns, Bletilla striata (Thunb.) Rchb. f., Atractylodes macrocephala Koidz., Ampelopsis japonica (Thunb.) Makino, Paeonia lactiflora Pall. (white), and Bombyx mori Linnaeus. Skin whitening prescriptions included multiple traditional Chinese medicinal materials. Despite the long history of use, there is a lack of studies concerning skin whitening products, possibly due to the complex composition of traditional Chinese medicine. Further studies are required to assess the efficacy and safety of these traditional Chinese medicinal materials for inclusion in effective, safe, and functional pharmacological products. Copyright © 2021 Ko, Chao, Chen, Su, Maeda, Lin, Chiang and Huang.