Anti-ulcerogenic Effect and HPLC Analysis of the Caffeoylquinic Acid-Rich Extract from Ligularia stenocephala

Abstract

Peptic ulcers can be caused by food, stress, genetic, and environmental factors, 1) including Helicobacter pylori infection, abuse of steroidal-or non-steroidal anti-inflammatory drugs (NSAIDs), irregular eating habits, smoking, alcohol consumption, and psychological stress.2) Peptic ulcers result from defects in the mucosa and muscularis mucosa, as well as oxidative stress due to the increase of reactive oxygen species (ROS). 3) In Korea, the leaves of Ligularia stenocephala MATSUM. et KOIDZ. (Family Compositae) are consumed as an edible vegetable and used as a Chinese folk medicine for the treatment of edema and scrofula. 4) In eastern and western Asia, the genus Ligularia is used for the treatment of influenza, cough, ulcer, and tuberculosis. 5) Yoon et al. have reported that the leaf extract of L. stenocephala showed the highest antithrombotic activity among large numbers of edible and herbal plants.6) The root of L. stenocephala contain benzofuran derivatives (ligulachepalins, euparin, hydroxytremetone, 7) 5,6-dimethoxy-2-isopropenylbenzofuran, 8) and stenocephalain, 9) as well as two caffeoylquinic acid derivatives, 3,4-dicaffeoylquinic acid and 3,5-dicaffeoylquinic acid).6) However, caffeoylquinic acid levels of those plants have not been studied.Although L. stenocephala has been traditionally used to treat gastric cancer or gastric ulcers, these biological activities have not been scientifically verified. Therefore, we intended to find the preventive activity of the caffeoylquinic acid-rich fraction with potent peroxynitrite scavenging effect on the ulcers induced by HCl/ethanol-and indomethacin/ bethanechol-induced in mice. In addition, we attempted to find whether or not the wild vegetables such as Ligularia species containing high level of caffeoylquinic acids are beneficial for ulcer disease. The methanolic extract of L. stenocephala together with its BuOH-and Et 2 O soluble fractions were evaluated for their anti-ulcerogenic activity using mice, with the BuOH extract showing the best activity. The BuOH fraction contained 5-O-caffeoylquinic acid, 3,5-di-O-caffeoyl-muco-quinic acid, and 3,5-di-O-caffeoylquinic acid from HPLC analytical data.In Korea, three Ligularia species, Ligularia stenocephala, L. fischeri, and L. fischeri var. spiciformis, are used as edible vegetables. The three herbs are similar taxonomically and are called gondalbi, gomchwi and numchwi, respectively, in Korea. Distinguishing these species may be improved with HPLC chromatograms. Other Compositae family members also contain caffeoylquinic acids, including Aster species, 10) and Solidago species, 5,11) as well as L. stenocephala, 6) and L. fischeri var. spiciformis. 11)Caffeoylquinic acid chemically consists of the two parts of quinic acid moiety and phenylpropanoid moiety. The most common parent skeleton of those compounds is quinic acid while muco-quinic acid or epi-quinic acid are also uncommonly found. The most common phenylpropanoid is caffeic acid while the less common ones are p-coumaric acid and ferulic acid. Caffeoylqui...

Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid

“…Caffeoyl moieties were easily recognized in the 1 H NMR spectrum as doublets in δ 7.60 and 6.30 (J = 16 Hz), together with several multiplets around δ 7.00, 6.90, and 6.80. The protons at δ 7.60 showed correlations in the HSQC spectrum with carbons at δ 146.6 and cross-peaks in the HMBC with carbons at δ 115.30, 123.20, and 169.70, consistent with data for caffeoylquinic acids (Lee et al 2010). The integration of a proton at δ 5.40 (H-1, sucrose) and protons at δ 6.20-6.45 (caffeoyl groups) was 1:0.6, respectively.…”

Protective effects of a triple‐fermented barley extract (FBe) against HCl/EtOH‐induced gastric mucosa damage in mice

“…Gastric mucosa damage can be easily produced by the generation of toxic free radicals (Biswas et al, 2003;Naito et al, 1995) and disorders or decreases in gastric mucosa antioxidant defense systems have been involved in the pathogenesis and progression of gastric ulcers (Kwiecień et al, 2002). EtOH is often used to induce gastric ulcer in various model systems to study on the development of drug for human ulcerative disease (Szabo & Brown, 1987) and to evoke severe and rapid gastric damage together with administration of HCl (Alqasoumi et al, 2009;Huh et al, 2003;Lee et al, 2010;Oyagi et al, 2010). Various synthetic antiulcer drugs are currently available, and some of these including RA, are representative histamine H 2 receptor antagonists specifically used to cure gastric ulcers.…”

“…Use of EtOH in in vivo study for inducing gastric ulcer has been commonly used model systems to study on ulcerative pathogenesis and its curative measures (Szabo & Brown, 1987). In addition, to evoke severe and rapid gastric damage induced by EtOH, hydrochloric acid (HCl), which also involved in the progression and pathogenesis of gastric damages, has been additionally administered (Alqasoumi et al, 2009;Huh et al, 2003;Lee et al, 2010;Oyagi et al, 2010). Therefore, administration of the HCl/EtOH mixture has been used as a valuable and simple method to study both the pathogenesis of and the therapy for human ulcerative disease in mouse gastric ulcer models, especially to study natural products based on their potent antioxidant effects (Murata et al, 2012;Niero et al, 2012;Oyagi et al, 2010;Yang et al, 2012).…”

Therapeutic effects of Ligularia stenocephala against inflammatory bowel disease by regulating antioxidant and inflammatory mediators

“…The leaves of Ligularia stenocephala (LS) are consumed as an edible vegetable and known as gondalbi in Korea. The genus Ligularia is usually treated as folk medicine to cure influenza, asthma, cough, ulcers, arthritis and tuberculosis (Lee et al, 2010) in some region of eastern and western Asia. Yoon et al (2008) reported the antithrombotic activity of the leaf extract of LS.…”