Hyperforin (dicyclohexylammonium salt) is a main active constituent of St. John's wort. Hyperforin activates the transient receptor potential canonical 6 (TRPC6) channels[1-2]. Hyperforin exhibits multiple biological activities and can be used in research related to diseases such as depression and cancer[3-4].
In vitro, Hyperforin (2–5μM) treated A375, FO1, and SK-Mel-28 human melanoma cells for 24–72 hours. Hyperforin significantly reduced cell viability, inhibited cell proliferation, and induced multiple forms of programmed cell death including cell cycle arrest, apoptosis, autophagy, and ferroptosis[5]. Hyperforin (5–10μM) treated HT-29 and HCT-116 human colorectal cancer cells for 48 hours. Hyperforin significantly induced cytotoxicity and apoptosis (including activation of the extrinsic and intrinsic apoptosis pathways), while also inhibiting the invasion and migration capabilities of the cells[6].
In vivo, Hyperforin (5mg/kg/day; administered intraperitoneally for 7 consecutive days) treated BALB/c mice induced with IMQ cream. Hyperforin significantly improved psoriasiform skin lesions such as erythema, scaling, and thickening, reduced epidermal thickness and pathological scores, suppressed the expression of pro-inflammatory cytokines in the skin, and alleviated IMQ-induced splenomegaly as well as serum levels of TNF-α and IL-6[7]. Hyperforin (0.5μg/μL; 1μL/day administered intracerebroventricularly; from 7 days before until 7 days after BCCAO surgery; for a total of 15 days) treated mice with BCCAO-induced vascular cognitive impairment. Hyperforin significantly improved cognitive function in the mice, attenuated white matter lesions in the hippocampus and corpus callosum, and inhibited microglial activation and the expression of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α in the hippocampus[8].
References:
[1] Heiser JH, Schuwald AM, Sillani G, et al. TRPC6 channel-mediated neurite outgrowth in PC12 cells and hippocampal neurons involves activation of RAS/MEK/ERK, PI3K, and CAMKIV signaling. J Neurochem. 2013 Nov;127(3):303-13.
[2] Pochwat B, Szewczyk B, Kotarska K, et al. Hyperforin Potentiates Antidepressant-Like Activity of Lanicemine in Mice. Front Mol Neurosci. 2018 Dec 12;11:456.
[3] Adam P, Arigoni D, Bacher A, et al. Biosynthesis of hyperforin in Hypericum perforatum. J Med Chem. 2002 Oct 10;45(21):4786-93.
[4] Li XX, Yan Y, Zhang J, et al. Hyperforin: A natural lead compound with multiple pharmacological activities. Phytochemistry. 2023 Feb;206:113526.
[5] Cardile A, Zanrè V, Campagnari R, et al. Hyperforin Elicits Cytostatic/Cytotoxic Activity in Human Melanoma Cell Lines, Inhibiting Pro-Survival NF-κB, STAT3, AP1 Transcription Factors and the Expression of Functional Proteins Involved in Mitochondrial and Cytosolic Metabolism. Int J Mol Sci. 2023 Jan 9;24(2):1263.
[6] Hsu LC, Kuo CY, Hsu FT, et al. Hyperforin Suppresses Oncogenic Kinases and Induces Apoptosis in Colorectal Cancer Cells. In Vivo. 2023 Jan-Feb;37(1):182-189.
[7] Zhang S, Zhang J, Yu J, et al. Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A-Producing γδ T Cells. Front Immunol. 2021 May 5;12:635076.
[8] Gao X, Chen J, Yin G, et al. Hyperforin ameliorates neuroinflammation and white matter lesions by regulating microglial VEGFR2 /SRC pathway in vascular cognitive impairment mice. CNS Neurosci Ther. 2024 Mar;30(3):e14666.
Hyperforin (dicyclohexylammonium salt)是一种贯叶金丝桃（St. John's wort）的主要活性成分，可激活瞬时受体典型6（TRPC6）通道[1-2]。Hyperforin具有多种生物学活性，可用于抑郁症、癌症等疾病的相关研究[3-4]。
在体外，Hyperforin（2–5μM）处理A375、FO1和SK-Mel-28人黑色素瘤细胞24–72小时。Hyperforin显著降低细胞活力、抑制细胞增殖并诱导细胞周期阻滞、凋亡、自噬和铁死亡等多重程序性细胞死亡[5]。Hyperforin（5–10μM）处理HT-29和HCT-116人结直肠癌细胞48小时。Hyperforin显著诱导细胞毒性和凋亡（包括激活外在/内在凋亡通路），同时抑制细胞的侵袭和迁移能力[6]。
在体内，Hyperforin（5mg/kg/day；连续7天腹腔注射）处理经IMQ乳膏诱导的BALB/c小鼠。Hyperforin显著改善了皮肤红斑、鳞屑和增厚等银屑病样病变，降低了表皮厚度和病理评分，同时抑制了皮肤中促炎细胞因子的表达，并减轻了IMQ诱导的脾肿大及血清中TNF-α和IL-6的水平[7]。Hyperforin（0.5μg/μL；每日1μL脑室内注射；从双侧颈总动脉闭塞手术前7天持续至术后7天；共15天）处理BCCAO诱导的血管性认知障碍小鼠。Hyperforin显著改善了小鼠的认知功能，减轻了小鼠海马和胼胝体的白质病变，并抑制了海马区小胶质细胞的活化及IL-1β、IL-6、TNF-α等促炎细胞因子的表达[8]。