Aromatic and Aliphatic Apiuronides from the Bark of Cinnamomum cassia

Abstract

Cinnamomum cassia Presl (Cinnamon) has been widely cultivated in the tropical or subtropical areas, such as Yunnan, Fujian, Guandong, and Hainan in China, as well as India, Vietnam, Thailand, and Malaysia. Four new glycosides bearing apiuronic acid (1, 4, 6, and 7) and their sodium or potassium salts (2, 3, and 5), together with 31 known compounds, were isolated from a hot water extract of the bark of C. cassia via repeated chromatography. The structures of the new compounds (1−7) were determined by NMR, IR, MS, and ICP-AES data and by acid hydrolysis and sugar analysis. This is the first report of the presence of apiuronic acid glycosides. Some of the isolates were evaluated for their analgesic effects on a neuropathic pain animal model induced by paclitaxel. Cinnzeylanol (8), cinnacaside (9), kelampayoside A (10), and syringaresinol (11) showed analgesic effects against paclitaxelinduced cold allodynia.A member of the Lauraceae family, Cinnamomum cassia Presl (Cinnamon) is a medium sized evergreen tree. 1 C. cassia originated in Southern China and can be widely cultivated in the Yunnan, Fujian, Guandong, and Hainan provinces of China, as well as in Thailand, Malaysia, Laos, India, Indonesia, and Vietnam. 2 Chinese cinnamon has been commonly used for centuries as a flavoring agent for desserts, pastries, and meat in Asia, Europe, and the Americas. 3 The bark of C. cassia (cinnamon) has been used as a traditional medicine to treat amenorrhea, gastrointestinal neurosis, cardiac palpitations diarrhea, edema, dysmenorrhea, rheumatoid arthritis, impotency, and diabetes. 4−6 The aqueous extract of cinnamon has been reported to exhibit potent anticomplement, immunosuppressive, antioxidant, antiproliferative, angiogenesis, antinociceptive, and anti-inflammatory activities and induced apoptosis. 7−13 The bark of C. cassia represents one of the major sources of phenolic compounds, and there are various secondary metabolites such as diterpenoids, 14−16 phenylpropanoids, 17−19 flavonoids, 20 lignans, 20,21 sesquiterpenoids, 22 and other compounds. 23,24 In a previous study, it was found that a hot water extract of the bark of C. cassia exhibited a relieving effect on cold allodynia induced by anticancer drugs. It was found that a major compound in C. cassia, coumarin, played a role in this analgesic effect. 25 Thus, we focused on secondary metabolites in the hot water extract with ameliorating effects against cold allodynia induced by paclitaxel in mice in the present work.Four new glycosides bearing apiuronic acid moieties (1, 4, 6, and 7) and their sodium or potassium salts (2, 3, and 5), together with 31 known compounds, were isolated from the hot water extract of the bark of C. cassia via repeated chromatography. The structures of the new compounds and their sodium or potassium salt forms were elucidated using spectroscopic [ 1 H NMR, 13 C NMR, 2D NMR, MS, IR, and inductively coupled plasma atomic emission spectroscopy (ICP-AES)] data, and the structures of the known compounds were identified by comparing spectroscop...

Bioactive Phenylpropanoid Glycosides, Dimers, and Heterodimers from the Bark of Cinnamomum cassia (L.) J.Presl

“…Considering the large coupling values of H-7/8 ( 3 , J H‑7–H‑8 = 16.2 Hz; 4 , J H‑7–H‑8 = 15.9 Hz), their aglycones were trans -cinnamic acid and trans -cinnamic alcohol, respectively. A precise comparison of their 1D NMR data with those of 1 , 2 , and glycosides recorded in refs and and acid hydrolysis indicated that 3 and 4 had 6- O -(β- erythro - d -apiofuranosyl)-β- d -glucopyranosyl and 6- O -(β -erythro - d -apiofuranuronyl)-β- d -glucopyranosyl, respectively. As we know, d -glucuronic acid is generated via oxidation of d -glucose catalyzed by the key enzymes UDP-glucose dehydrogenase/ myo -inositol oxygenase. , Correspondingly, we also suggest that β -erythro - d -apiofuranuronyl in 4 is produced by the oxidation of β- erythro - d -apiofuranosyl catalyzed by potential dehydrogenase/oxygenase (apiofuranosyl in 1 – 3 was β- erythro - d -apiofuranosyl).…”

“…Six known relevant compounds, cryptamygin C ( 15 , CAS: 475632-39-4), methyl 2-[6- O -(β- erythro - d -apiofuranosyl)-β- d -glucopyranosyloxy]-dihydrocinnamate ( 16 , CAS: 1818196-70-1), cinnacassioside B ( 17 , CAS: 2763825-48-3), 7- O -β- d -glucopyranosyl-phenylmethanol ( 18 , CAS: 4304-12-5), (2 R *,3 R *)-5,7-dimethoxy-3′,4′-methylenedioxy-epicatechin ( 19 , CAS: 87562-72-9), and (2 R *,3 R *)-5,7,3′-trimethoxy-epicatechin ( 20 , CAS: 2518186-98-4) were identified by comparison of their spectroscopic data recorded in the literature.…”

Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal Microglia

“…Syringaresinol was obtained as previously described [ 36 ]. In brief, the dried Cinnamomum cassia bark (6.0 kg) was extracted with hot water (60 L, 100 °C) twice in water bath for 2 h and the solvent was vaporized at 45 °C in vacuo.…”

“…Syringaresinol directly affects microglia and macrophages to modulate the production of NO and related proteins, such as iNOS, and downregulates inflammatory signaling via the MAPKs pathway [ 22 , 33 , 34 , 35 ]. In our previous study, we investigated the analgesic effects of syringaresinol isolated from the bark of Cinnamomum cassia (Cinnamomi Cortex) on neuropathic pain induced by paclitaxel [ 36 ]. We also found that Cinnamomi Cortex has analgesic efficacy against OIPN [ 21 ].…”

Analgesic effects of medicinal plants and phytochemicals on chemotherapy‐induced neuropathic pain through glial modulation

“…Recent research has revealed that medicinal herbs have various pharmacological activities, such as antimicrobial, antioxidant, anti‐inflammatory, and anti‐nociceptive activities 19 . The potency of medicinal herbs is mediated by their bioactive compounds and phytochemicals 20–22 …”