The anti-inflammatory alkaloid aloperine in Chinese herbal medicine is potentially useful for management of pain and itch

Tianle Gao; Malin C. Lagerström

doi:10.1016/j.sjpain.2015.04.025

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The anti-inflammatory alkaloid aloperine in Chinese herbal medicine is potentially useful for management of pain and itch

Tianle Gao and Malin C. Lagerström

Published/Copyright: July 1, 2015

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From the journal Scandinavian Journal of Pain Volume 8 Issue 1

In this issue of the Scandinavian Journal of Pain, Yang and co-workers report interesting effects of aloperine on acute and inflammatory pain behaviour in mice [1]. Aloperine is an alkaloid isolated from the plant Sophora alopecuroides L that, as indicated by preclinical evidence, possesses anti-inflammatory and anti-allergic properties [2]. In the Yang and co-workers’ study, aloperine’s analgesic efficacies were determined by performing behavioural tests of acute and inflammatory pain, and the authors documented that aloperine can suppress pain-like behaviours in several inflammatory pain models in mice [1].

In acetic acid-induced writhing test, aloperine (40 mg/kg or 80mg/kg) had an anti-nociceptive effect and reduced the writhing behaviours. However, compared with morphine (10 mg/kg), which almost completely inhibited the writhing response, the effects of these doses of aloperine were minor [1]. Similarly, aloperine was found to be able to dose-dependently suppress formalin-induced pain behaviour, both in the first and second phases, while aspirin was only effective in the second phase [1]. Furthermore, the ear swelling test and carrageenan-induced paw oedema test documented aloperine’s suppressing effect on inflammation. In these tests, aloperine was found to suppress the pro-inflammatory cytokines tumour necrosis factor, Interleukin-1 beta, and prostaglandin E2, as well as enhancing the production of anti-inflammatory cytokine interleukin-10, in the inflamed tissues [1].

1 Similarities between sinomenine and aloperine, two alkaloids from traditional Chinese herbal medicine

In this respect, the anti-inflammatory effects, aloperine is similar to sinomenine, which is an alkaloid purified from the plant Sinomenium acutum that also possesses analgesic efficacy against inflammatory pain behaviour [3,4]. However, unlike sinomenine [5], aloperine failed to illicit any anti-nociception on thermal-stimulated acute pain, assessed by using the hot plate test and the tail flick test [1]. The capability of aloperine to diminish neuropathic pain induced by chronic constriction injury was reported by the same group in 2014, and they proved that the anti-nociceptive effects of aloperine against neuropathic pain is related to reduction of reactive oxygen species (ROS) by suppressing the NF-κB pathway in the central nervous system [6]. Surprisingly again, aloperine is similar to sinomenine in terms of analgesic efficacy against neuropathic pain behaviour [3,7] and inhibition of ROS [8].

2 The success of searching for new analgesic substances intraditional Chinese herbal medicine

There are several advantages from studying single molecules isolated from natural, herbal medicines (such as aloperine and sinomenine) as potential drug candidates. The most crucial benefit is that the original herbs have been used for hundreds or even thousands of years, and this indicates that the molecules are well tolerated by humans. As indicated, the clinical safety profiles for aloperine and sinomenine are both positive, with few and relatively mild side effects that are generally reversible [3,9]. Similarly, in the current study the effective dosage of aloperine did not cause any sedation or motor deficit in animals [1], and the same is also true for sinomenine . Beside the issue of toxicity, the drug application routes for molecule from natural medicines are more flexible, since they are usually orally effective, and they can be applied topically. In addition, in majority of the cases, their effective dosage windows are quite broad, which allows the patients to adjust the doses needed without reaching a level limited by toxicity. However, there are challenges as well. It is not easy to identify the site of drug action and the exact drug target.

3 Site and mechanisms of analgesic effect?

It is important to know the action site of a new analgesic; pain modulation is different at different levels of the somatosensory nervous system. In the present study, the authors studied the effect of aloperine on pain-like responses on behaviour of experimental animals to chemical or thermal stimulation. However, Yang and co-workers were not able to document where the analgesic effect of aloperine takes place; we do not know if it is peripheral or within the central nervous system. For assessment of the site of action, they could have compared e.g. the analgesic effects induced by peripheral, spinal cord, or intracerebral injections of aloperine. They could have assessed responses of nociceptive neurons at different levels of the neuraxis.

Patients with chronic nociceptive pain often also suffer from depression and anxiety [10]. Therefore, it would be beneficial for chronic pain patients to co-administer drugs that suppress peripheral nociceptors and spinalcord pain relay-neurons, with drugs that improve affective responses to nociceptive stimuli at supra-spinal levels.

For molecules extracted and purified from traditional medicines it is also important to know the exact target; is it a receptor, an enzyme, or a transcription factor? In which cell type(s) does the target reside; is it located in the immune cells or in neuronal cells? When considering combining newly identified analgesic drugs with existing therapies, this is key information for evaluating potential synergy and reduction in side effects from such combinations.

4 Pain and itch are linked in neuronal pathways and aloperine appears to have beneficial effects on both symptoms

Interestingly, aloperine-containing herbal medicine has been widely used in China for treating allergic contact dermatitis, atopic dermatitis, eczema, and other skin conditions with inflammatory components where itching is a major symptom [9,11]. Since the neuronal circuit of itch and pain are related [12,13], and the release of the itch-inducing substance histamine can be suppressed by aloperine during inflammation [2], it is reasonable to expect that aloperine modulates itch in such skin diseases. Pain is a common and often neglected part of the suffering of patients with chronic skin-diseases [14].

To conclude, aloperine, analkaloid purified from traditional Chinese herbal medicine, has potential to be therapeutic in various pain conditions. Aloperine may be especially beneficial for patients suffering pain and itch from various skin-diseases.

DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2015.04.001

Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz Väg 2, 17177 Stockholm, Sweden. Tel.:+46 8 5248 7935

Conflict of interest: The authors declare no conflict of interests.

References

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Published Online: 2015-07-01

Published in Print: 2015-07-01

Articles in the same Issue

https://doi.org/10.1016/j.sjpain.2015.04.025