Introduction AR36 is a pharmaceutical-grade plant extract used to support cardiovascular health in traditional Chinese medicine. Studies suggest that AR36 may prevent acute mountain sickness (AMS) during gradual ascent to high altitude. This randomized, placebo-controlled Phase 2 trial aimed to evaluate dosing regimens and assess efficacy and safety of AR36 for AMS prevention during rapid ascent. Methods Participants received placebo, low-dose AR36 (225 mg twice daily for 14 d prior and 5 d at altitude), or high-dose AR36 (12 d placebo, 300 mg twice daily for 2 d prior and 5 d at altitude). The primary efficacy outcome was 1993 Lake Louise Scoring System (LLSS) score on the morning after ascent. Safety was assessed through the proportion of treatment-emergent adverse events (TEAEs). Results One hundred thirty-two participants were randomized. Mean±SD age was 31.4±8.6 (range, 19–54) y. Baseline characteristics did not differ across groups. Lake Louise Scoring System scores on Day 16 in the placebo, low-dose, and high-dose groups were 4.03 (2.88), 4.42 (3.17), and 3.5 (2.31), respectively (placebo versus low-dose, P=0.462; placebo versus high-dose, P=0.574; n=110). The incidence of AMS on Day 16 was 66.7% in the placebo, 61.1% in the low-dose, and 55.3% in the high-dose group ( P=0.66). The proportion of TEAEs in the placebo, low-dose, and high-dose groups was 38.4% (81), 28.4% (60), and 33.2% (70), respectively ( P=0.205; n=127). There was no statistical difference between groups in LLSS, incidence of AMS, or TEAEs. Conclusions AR36 did not improve LLSS or AMS incidence using the current regimens. AR36 was well tolerated.

2014-04-01·Molecular Plant1区 · 生物学

New Strigolactone Analogs as Plant Hormones with Low Activities in the Rhizosphere

1区 · 生物学

Article

作者: Christian V. Stevens ; Jean-Paul Pillot ; Jean-Bernard Pouvreau ; Catherine Rameau ; Sofie Goormachtig ; François-Didier Boyer ; Amanda Rasmussen ; Nicolas Frei dit Frey ; Dominique Lauressergues ; Guillaume Clavé ; Alexandre de Saint Germain ; Amélie Roux ; Danny Geelen ; Stephen Depuydt ; Thomas S.A. Heugebaert

Strigolactones (SLs) are known not only as plant hormones, but also as rhizosphere signals for establishing symbiotic and parasitic interactions. The design of new specific SL analogs is a challenging goal in understanding the basic plant biology and is also useful to control plant architectures without favoring the development of parasitic plants. Two different molecules (23 (3'-methyl-GR24), 31 (thia-3'-methyl-debranone-like molecule)) already described, and a new one (AR36), for which the synthesis is presented, are biologically compared with the well-known GR24 and the recently identified CISA-1. These different structures emphasize the wide range of parts attached to the D-ring for the bioactivity as a plant hormone. These new compounds possess a common dimethylbutenolide motif but their structure varies in the ABC part of the molecules: 23 has the same ABC part as GR24, while 31 and AR36 carry, respectively, an aromatic ring and an acyclic carbon chain. Detailed information is given for the bioactivity of such derivatives in strigolactone synthesis or in perception mutant plants (pea rms1 and rms4, Arabidopsis max2 and, max4) for different hormonal functions along with their action in the rhizosphere on arbuscular mycorrhizal hyphal growth and parasitic weed germination.

Frontiers in Plant Science2区 · 生物学

Methylation at the C-3′ in D-Ring of Strigolactone Analogs Reduces Biological Activity in Root Parasitic Plants and Rice

2区 · 生物学

ArticleOA

作者: Jamil, Muhammad ; Ota, Tsuyoshi ; Zarban, Randa A ; Wang, Jian You ; Kountche, Boubacar A ; Asami, Tadao ; Haider, Imran ; Arold, Stefan T ; Takahashi, Ikuo ; Jia, Kun-Peng ; Al-Babili, Salim ; Aldossary, Faisal ; Shahul Hameed, Umar F ; Yonli, Djibril

Strigolactones (SLs) regulate plant development and induce seed germination in obligate root parasitic weeds, e.g. Striga spp. Because organic synthesis of natural SLs is laborious, there is a large need for easy-to-synthesize and efficient analogs. Here, we investigated the effect of a structural modification of the D-ring, a conserved structural element in SLs. We synthesized and investigated the activity of two analogs, MP13 and MP26, which differ from previously published AR8 and AR36 only in the absence of methylation at C-3'. The de-methylated MP13 and MP26 were much more efficient in regulating plant development and inducing Striga seed germination, compared with AR8. Hydrolysis assays performed with purified Striga SL receptor and docking of AR8 and MP13 to the corresponding active site confirmed and explained the higher activity. Field trials performed in a naturally Striga-infested African farmer's field unraveled MP13 as a promising candidate for combating Striga by inducing germination in host's absence. Our findings demonstrate that methylation of the C-3' in D-ring in SL analogs has a negative impact on their activity and identify MP13 and, particularly, MP26 as potent SL analogs with simple structures, which can be employed to control Striga, a major threat to global food security.

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适应症	最高研发状态	国家/地区	公司	日期
心血管疾病	临床3期	-	Arbor Pharmaceuticals LLC	-
呼吸障碍	临床前	美国	Arbor Pharmaceuticals LLC	2021-04-13
心绞痛	临床前	美国	Arbor Pharmaceuticals LLC	2018-11-08