Chuanxiongdiolides R4 and R5, phthalide dimers with a complex polycyclic skeleton from the aerial parts of Ligusticum chuanxiong and their vasodilator activity

A comprehensive investigation on the chemical diversity and efficacy of different parts of Ligusticum chuanxiong

“…The voucher specimens were deposited at the State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine. Four reference materials were purchased from Chengdu Pruifa Technology Development Co., Ltd (Chengdu, China), including 3 alkyl phthalide monomers, namely 3-butylphthalide, Z-ligustilide and Z-butylidenephthalide, and 1 phthalide dimer, levistolide A. Additionally, 18 phthalide compounds obtained from our previous studies 12,13 were also selected as reference materials, including 6 hydroxyl phthalide monomers, (3S,3aR,10R)-(−)-10-hydroxysedanolide, Z-senkyunolide E, senkyunolide F, senkyunolide C, 4-hydroxy-butylidenephthalide and 2-(1-oxopentyl)-benzoic acid methyl ester, and 12 phthalide dimers, including chuanxiongdiolide R1, 4,5-dehydro-diligustilide, methyl ester derived from angeolide, 6.8′,7.3′-diligustilide, (3Z)-(3aR,6S,3′R,8S)-3a.8′,6.3′-diligustilide, diangeliphthalide A, tokiaerialide, chuanxiongdiolide R6, chuanxiongdiolide R4, chaxiongnolide D, Z,Z'-3.3′a,7.7′a-diligustilide and chuanxiongdiolide R5. These compounds showed no less than 95% purity by HPLC, and the chemical structures of 22 reference compounds are shown in Fig.…”

“…In vitro vasodilator activity assay. The vasodilator activity assay was carried out as described as Tang et al 12 SD rats were sacrificed using 10% chloral hydrate, and the thoracic aorta was separated, and the connective tissue was cleaned up and cut into 4-5 millimeter long rings. The aortic rings were fixed with a steel hook and suspended in organ baths containing 20 mL Krebs solution [composition (mM): 120 mM NaCl, 4.6 mM KCl, 1.2 mM KH 2 PO 4 , 1.2 mM MgSO 4 , 25 mM NaHCO 3 , 10 mM glucose and 2.5 mM CaCl 2 ] at 37 °C.…”

“…Among them, the characteristic ion at m/z 193. 12 ] + were observed in peaks 85, 89 and 92, suggesting that the monomers units of peaks 58 and 67 were senkyunolide A coupled with senkyunolide A (type F), and peaks 85, 89 and 92 were ligustilide coupled with neosolactone (type E) (Table S4 †). Based on the candidate structures in the internal database, peaks 58 and 67 were tentatively identified as 3,8-dihydro-diligustilide 21 or chuanxiongdiolide A.…”

“…11 Our previous studies showed that the phthalide dimers in the stems and leaves of CX can be used as novel vasodilators, which further highlighted the value of the development and utilization of its non-medicinal parts. 12,13 However, the chemical components of CX are still lacking in the systematic reviews, and the functional differences of different anatomical parts of CX in preventing cardiovascular and cerebrovascular diseases are still unclear.…”

Research Advances in Cardio-Cerebrovascular Diseases of Ligusticum chuanxiong Hort.

“…Compared with the rhizomes, only the content is different (Jiang et al, 2008). In the Bencao Huiyan, the aboveground part of CX is called "Mi Wu," accounting for 75% of the fresh weight of the whole plant (Jiang et al, 2008;Tang et al, 2021). At the same time, CX is also one of the drugs that can be used for health food announced by the Ministry of Health of China in 2017 (Yu, 2017).…”