Elsevier

Journal of Ethnopharmacology

Volume 151, Issue 2, 3 February 2014, Pages 944-950
Journal of Ethnopharmacology

Research Paper
Antinociceptive and anti-inflammatory activities of extract and two isolated flavonoids of Carthamus tinctorius L

https://doi.org/10.1016/j.jep.2013.12.003Get rights and content

Abstract

Ethnopharmacological relevance

Safflower (Carthamus tinctorius L.) has been long used both in the traditional system and folk medicine as an analgesic anti-inflammatory agent in China. The aim of the study was to evaluate the antinociceptive and anti-inflammatory activities of hydroalcoholic extract (HE) and two isolated kaempferol glycosides of Carthamus tinctorius L. to provide experimental evidence for its traditional use.

Materials and methods

Antinociceptive effects of HE, kaempferol 3-O-rutinoside (K-3-R) and kaempferol 3-O-glucoside (K-3-G) were assessed in mice using the acetic acid-induced writhing test, formalin test and cinnamaldehyde test. The anti-inflammatory effects of HE, K-3-R and K-3-G were determined in two animal models: carrageenan-induced paw edema and xylene-induced ear edema.

Results

The HPLC analysis showed the presence of K-3-R and K-3-G in Carthamus tinctorius L. HE (500 and 1000 mg/kg) as well as K-3-R and K-3-G (150, 300 and 600 mg/kg) produced significant inhibition on nociception induced by acetic acid and formalin. Oral treatment of HE, K-3-R and K-3-G at all doses significantly reduced both the nociceptive response and cinnamaldehyde-induced paw edema, effect that was superior to aspirin. In anti-inflammatory tests, HE and K-3-G significantly inhibited the paw edema during the both phases of carrageenan-induced inflammation while K-3-G suppressed the late phase inflammation only. HE (400 and 800 mg/kg) and K-3-G (200, 400, 800 mg/kg) produced significant dose-dependent inhibition of xylene-induced ear edema development. K-3-R only suppressed ear edema formation at a high dose (800 mg/kg).

Conclusions

These results demonstrate that Carthamus tinctorius L. extract possess remarkable antinociceptive and anti-inflammatory activities which may be due to K-3-R and K-3-G at least in part, supporting the folkloric usage of the plant to treat various inflammatory and pain diseases.

Introduction

Inflammation is an immunological defense mechanism elicited in response to mechanical injuries, burns, microbial infections, allergens and other noxious stimulus (Yoon and Baek, 2005). It develops in the classical forms of redness, swelling, heat and hyperalgesia. These symptoms result from the action of inflammatory agents such as bradykinin, serotonin, histamine, prostaglandins, leukotrienes and nitric oxide, which can originate locally or from cells that infiltrate in the site of insult (Li et al., 2011). Pain is a common symptom of various inflammatory diseases and an unpleasant sensory experience associated with actual or potential tissue damage (IASP, 1979, Silva et al., 2010). Frequently, tissue damage leads to activation of nociceptors through the release of a variety of chemical mediators, such as excitatory amino acids, protons, peptides, lipids and cytokines, among others, which act on specific receptors and ion channels, contributing to the induction of pain and inflammation (Sawynok, 2003, Cunha et al., 2005). Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed therapeutics, primarily for the treatment of pain and inflammation. However, long-term clinical usage of NSAIDs is associated with significant side effects, such as gastrointestinal lesion, bleeding and peptic ulcers (Corley et al., 2003). As an alternative, plant based medicines are getting an increased therapeutics market share due to their mild action and fewer adverse effects.

Safflower (Carthamus tinctorius L.), a member of Asteraceae family, is a traditional medicinal and edible plant used for a long history that promotes blood circulation to remove blood stasis and alleviate pain. In China safflower injection has been used clinically for cerebrovascular disease, coronary heart disease, and angiitis (Li et al., 2009). Further studies revealed that the plant possesses anti-inflammatory activity (Lee et al., 2009, Jun et al., 2011) but researches have tended to focus on its mixed extracts and only a few have been investigated in detail.

Kaempferol, the most common flavonols present in different glycosidic forms in several plants, including Carthamus tinctorius L., has also been used as a phytochemical marker and legal standard for qualitative and quantitative studies of safflower flowers in Chinese Pharmacopoeia, 2010 in China. There are quite a few studies reporting the antinociceptive and anti-inflammatory effects of kaempferol glycosides (Orhan et al., 2007, De Melo et al., 2009, Bhouri et al., 2011).

In our study, two kaempferol glycosides were isolated from safflower flowers: kaempferol 3-O-rutinoside (K-3-R) and kaempferol 3-O-glucoside (K-3-G). To our knowledge, there is comparatively little information about the functional roles of these two single compounds (K-3-R and K-3-G) extracted from this traditional Chinese medicine. Considering the ethanobotanical uses of the plant in the treatment of pain and inflammation, and that one of the main constituents of the species are kaempferol glycosides, this study evaluated the in vivo antinociceptive and anti-inflammatory effects of hydroalcoholic extract (HE) obtained from safflower flowers and it isolated compounds (K-3-R and K-3-G), in order to justify the use of this plant as an analgesic anti-inflammatory agent in folk medicine.

Section snippets

Plant material

Flowers of safflower (Carthamus tinctorius L.) were harvested at Jianyang County (104.64°E, 30.43°N), Sichuan Province of China in June, 2011 and supplied by Sichuan Academy of Agricultural Science, China. The reference specimens were deposited at Department Pharmacognosy, West China School of Pharmacy, Sichuan University.

Extraction and isolation

Air dried and grounded (2000 g) flowerers of safflower were extracted with 75% EtOH (v/v) by percolation at room temperature. The hydroalcoholic percolate was evaporated under

HPLC analysis

The HPLC analysis showed the presence of K-3-R (Tr: 6.79 min) and K-3-G (Tr: 8.34 min) in the extract. The compounds were identified in comparison of their retention time and UV spectra with external standards (Fig. 2).

Acetic acid-induced writhing

The intraperitoneal administration of HE (500, 1000 mg/kg), K-3-R (150, 300, 600 mg/kg) and K-3-G (150, 300, 600 mg/kg) caused a significant reduction (P<0.001) dose dependently in the number of writhing episodes induced by acetic acid compared to the control by 64.01, 74.76, 71.01,

Discussion and conclusion

In the present study, the anti-nociceptive and anti-inflammatory effects of hydroalcoholic extract of Carthamus tinctorius L. and two kaempferol glycosides isolated from the plant, K-3-R and K-3-G were evaluated to justify its use in the traditional medicine.

The acetic acid-induced writhing, formalin and cinnamaldehyde test were used to investigate the in vivo anti-nociceptive activity of the extract and two isolated kaempferol glycosides. The acetic acid-induced writhing test is a visceral

Acknowledgments

This research was supported by Research Foundation for the Sichuan Science and Technology Support Programme of China (2011NZ0098-12-01).

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