Screening of Euphorbiaceae Plant Extracts for Anti-5α-reductase

Abstract

In our research program to find novel agents for alopecia from natural plant resources, we screened Euphorbiaceae plant extracts using an anti-5α-reductase assay. Among the samples tested, the extract of Phyllanthus urinaria showed the most potent activity with 24.3 and 64.6% inhibition at 50 and 200 µg/mL against the enzyme, respectively. The extract also suppressed the androgen activity of dihydrotestosterone in LNCaP cell line. These results show that the extract of P. urinaria may be a multi-potent agent for androgen-derived alopecia. We tested for activity on a hair regrowth model using mice. The extract of P. urinaria showed hair regrowth activity at 5 mg/mouse/d administration. Furthermore, the active principle for anti-5α-reductase activity was determined as stigmasterol glucoside from activity-guided fractionation and the IC 50 was 27.2 µM. These results suggest that extract of P. urinaria may be a promising candidate anti-alopecia agent.Key words 5α-reductase; androgen receptor; Euphorbiaceae; Phyllanthus urinaria; stigmasterol glucoside Hair loss is a major cosmetic problem in the prime of manhood, and may reduce QOL and lead to serious depression. Hair loss is mainly attributable to a change in testosterone level. Testosterone is a hormone in males that is dehydrolyzed to dihydrotestosterone by 5α-reductase, which is a more potent androgen than testosterone. Dihydrotestosterone strongly binds to androgen receptor and the complex migrates to the nucleus. This migration enhances the mRNA transcription of the anti-proliferative factor, transforming growth factor β (TGF-β) and suppresses the proliferation of hair follicle cells. Alopecia attributed to androgen is known as androgenetic alopecia and is recognized as a disease. Medical therapy for androgenetic alopecia is available; however, an alternative medicine for androgenetic alopecia using affordable self-care agents has long been awaited. In our research program to investigate hair growth agents from natural plant resources, we discovered that extracts from the flower of Pueraria lobata, 1) the leaves of Rosmarius officinalis2) and the rhizome of Panax ginseng 3) were effective for hair growth via their inhibition of 5α-reductase.In our research program to find effective plant materials from natural resources, we focused on Euphorbiaceae plants, which possess various active components and biological activities. [4][5][6] In addition, Euphorbiaceae plants have been said to be effective for burns to the skin since ancient times, which indicates cell proliferation activity. Thus, if a plant material extract has both cell proliferating and anti-5α-reductase activities, it may be a suitable agent for hair growth. In these circumstances, we screened 10 plant extracts for anti-5α-reductase activity and the active principles were determined.We selected plant samples randomly from Euphorbiaceae plants for screening as follows; whole plant of Phyllanthus urinaria, root of Glochidion eriocarpum, whole plant of Speranskia tuberculate, leaf of Breynia patens, wh...

Phytochemicals With Anti 5-alpha-reductase Activity: A Prospective For Prostate Cancer Treatment

“…Another PS, stigmasterol, was reported to be associated with a reduction in common cancer risks including colon cancer, breast cancer and CaP ( Bradford & Awad, 2007 ). Kamei et al (2018) studied Phyllanthus urinaria where the extract was shown to suppress androgen activity of DHT in LNCaP cell lines and has inhibitory activity against 5αRs, of which the active bioactive compound responsible for the activity was identified as stigmasterol isolated from an activity-guided fractionation. An in vitro study of Serenoa repens extract (SPE) using baculovirus-directed insect cell expression system demonstrated the inhibition of both 5αR1 and 5αR2 in a non-competitive and uncompetitive manner, respectively ( Iehlé et al , 1995 ).…”

The Lack of Standardization and Pharmacological Effect Limits the Potential Clinical Usefulness of Phytosterols in Benign Prostatic Hyperplasia

“…According to an in vitro study performed by Marisa Cabesa and her colleagues on hamster prostate tissue, SIT inhibits 5-αR in a dose-dependent manner (IC 50 = 1.1 µg/mL compared to finasteride with IC 50 = 0.003 µg/mL) [59]. Other data have shown that stigmasterol, extracted from Phyllanthus urinaria, also inhibits 5-αR and is less potent than SIT (IC 50 = 11.2 µg/mL) [60]. To offset the low efficacy of PSs, a combination of conventional treatments with PSs may provide some clinical benefit.…”