Dong-Jin Lee ¹, Min Hwangbo ², Kang Kwon ¹, Hyung-Sik Seo ^{1 *}

The endpoint of this review is to investigate existing studies of Cervi cornu parvum (CCP) pharmacopuncture within Korean medicine journals in order to present a better research method in the future.

We searched all the papers through six Korean electrical databases that included the title of "Cervi cornu parvum pharmacopuncture" or "Cervi cornu parvum aqua-acupuncture". Articles that had been published until December 2012 were largely divided into experimental studies and clinical studies.

Fifty-three (53) experimental studies and six clinical studies were found. The number of published articles has been constantly increasing. Many of the experimental studies demonstrated anti-inflammatory effects for arthritis, and most of the clinical studies dealt with musculoskeletal problems.

Various therapeutically significant effects of the CCP pharmacopuncture have been found through this review; however, more systematic clinical studies on the CCP pharmacopuncture seem to be necessary to substantially support its clinical effects.

aqua-acupuncture, Cervidae, deer antler, Korean medicine, pharmacopuncture, review

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Pharmacopuncture therapy is a treatment that is applied by injecting a certain amount of a herbal extract on an acupoint or a hypersensitive epidermal point [1]. It has been used as an identical term with "aqua-acupuncture" in the sense that it combines acupuncture and herbal medication. Recently, direct injection of herbal medicine into an affected tissue has drawn global attention and is thought to have the great merit of being able to enhance therapeutic effects even with small dosage [2].

Cervi cornu parvum (CCP) is a major blood-tonifying restorative traditional medicine that is commonly used nowadays as a pharmacopuncture material, and relevant clinical or experimental studies are continuously being reported. In this context, only two review papers concerning CCP, one in Korea and one overseas, respectively have been found. One is a biochemical and nutritional review [3], and the other is a review of deer antler base in Chinese literature [4].

To date, experimental and clinical studies have been undertaken to show the objective effects of CCP pharmacopuncture. Therefore, a review article addressing the objective effects of CCP pharmacopuncture is needed. Because of this, we analyzed existing research trends on CCP pharmacopuncture in Korean literature in the hope of finding better study methods and expanding the scope of clinical practice in the future.

This research was carried out by surfing the following Korean electric databases: Korean Traditional Knowledge Portal (KTKP), Oriental Medicine Advanced Searching Integrated System (OASIS), Research Information Services (RISS), Korean studies Information Service System (KISS), Korean Medicine Database and National Discovery for Science Leader (NDSL) (Table 1). Articles titled "CCP pharmacopuncture" or "CCP aqua-acupuncture" in Korean were included in the study. Additionally, papers including other treatments were selected if CCP pharmacopuncture had been used as a main intervention. This review only covers articles published until December 2012. Forty-nine CCP pharmacopuncture articles and ten CCP aqua-acupuncture articles were chosen for this study.

Fifty-nine (59) articles were found in 14 kinds of journals. Thirty-one (31) articles were found in the Journal of Korean Acupuncture & Moxibustion Medicine Society, which accounts for 53% of all articles, 5 articles each in the Journal of Pharmacopuncture and the Journal of Korean Oriental Medicine, 4 articles in the Journal of Oriental Rehabilitation Medicine, 3 articles each in the Korean Journal of Meridian & Acupoint and the Journal of Korean Oriental Internal Medicine, and one or two articles in the remaining journals (Table 2).

Beginning with 1 article in the 1960's, 1 article in the 1970's, 4 articles in the 1980's, 13 articles in the 1990's and 34 articles in the 2000's, the number of publications has been constantly increasing (Fig 1). There are 53 experimental articles and 6 clinical articles. Clinical articles consist of 4 case reports, one experiment-control group comparative study and one clinical trial.

Of the 53 experimental articles, 12 addresses the effect on arthritis-induced models [5-16], 9 articles address antiosteoporosis effects [17-25], and 6 anti-oxidation and antiaging effects [26-31]. In addition, 4 articles reported on safety studies [32-35], and 4 articles on the promotion of hormone production [36-39]. Furthermore, two articles each were published in the following areas: component analysis [40, 41], modulation of the autonomic nervous system [42, 43], anti-ischemic effects [44, 45], anti-cancer effects [46, 47], promotion of growth [48, 49], increased immunity [50, 51], and neuranagenesis [52, 53], for a total of 14 articles. Finally, one article was found in each of the following four areas for a total of four articles: analgetic effect [54], anti-stress effect [55], Sasang topology [56], and acupuncture sensation [57].

Of the six clinical studies [58-63], one is on otorhinolaryngological disease while the rest are all on musculoskeletal pain disease. Also, two studies were performed only with CCP pharmacopuncture whereas four studies combined pharmacopuncture with other traditional therapies.

In recent years, Korean medicine has been undergoing a variety of academic developments and studies on pharmacopuncture may be one of the conspicuous changes. Pharmacopuncture therapy, first introduced in Korea by the book named "Meridians" and written by Sang-chun Nam in the 1960's, is a unique treatment that combines the physical stimulation of classic acupuncture at valid acupoints with the pharmacological action of biochemical substances obtained from various herbs in order to alleviate symptoms and to prevent diseases by modulating the biofunction. From the late 1970's, active research in this field has been ongoing within Korean medicine community, and in 1991, the Korean Institute of Pharmacopuncture was established, thereby contributing more systematically to the development of pharmacopuncture.

Because of its convenience, accessibility and efficiency, pharmacopuncture is widely used by many doctors of Korean medicine and has great potential for the future [64]. Cervi cornu parvum (CCP), belonging to the Cervidae family, is an unossified horn that contains many vessels inside the tissue. It was first recorded in the Chinese medical classic Shen Nong Ben Cao Jing (神農本草經), in which it was described as having a warm nature, and a sweet taste; it was also reported to be non-toxic, to tonify the kidney yang, to replenish blood and essence, and to strengthen bones and muscles, thus, it has the ability to treat impotence, incontinence, infertility, aversion to cold, cold extremities, lower limb weakness, lumbar pain, tinnitus and gradual loss of hearing [65].

Also, immunity improvement, and anti-cancer, antifatigue, anti-stress, anti-oxidation, anti-inflammation and analgesic effects have been pharmacologically proven in many studies [4]. Furthermore, CCP helps to make up for deficiencies of qi, blood, Yin and Yang, allowing its use in treating a wide range of diseases.

CCP pharmacopuncture is a sort of meridian pharmacopuncture and is manufactured by the process of alcohol immersion. However, when it is exposed to air, it becomes fiberized, causing burning pain in the injected patients [1]. Although much research on CCP is available in Korean, not a single review article has been found yet in Korean literature. Wu et al. [4] recently reviewed deer antler base in Chinese literature while Kang et al. [3] reviewed only the biochemical and the nutritional parts of CCP, all of which had limitations on understanding the overall research trends of CCP pharmacopuncture in Korea. Thus, we collected all the relevant articles published until December 2012 and analyzed its research trends. This study processed 59 articles from 6 Korean electric databases. There were 53 experimental articles and 6 clinical articles. The number of experimental studies obviously overwhelmed that of clinical studies. Aquaacupuncture, so-called acupoint injection therapy in China, has the same meaning as pharmacopuncture by definition [66] and was also included as a search term. It is strongly recommended that these two terms be unified into pharmacopuncture in order to avert confusion.

Based on topics, experimental studies address the antiinflammation effect on arthritis (12 articles, 20%), antiosteoporosis effect (9 articles, 15%), anti-oxidation and antiaging effects (6 articles, 10%), and safety and increased hormone production (4 articles each, 7%). Two articles each (3%) were published on component analysis, autonomic nerve modulation, anti-ischemic effect, anti-cancer effect, increased immunity, growth promotion, and neuranagenesis effects. The remaining studies reported on different topics. On the other hand, clinical studies addressed musculoskeletal pain diseases (5 articles, 8%) and otorhinolaryngological disease (1 article, 2%) (Table 3).

Based on journals, The Journal of Korean Acupuncture & Moxibustion Medicine Society published 31 articles while the Journal of Pharmacopuncture and the Journal of Korean Oriental Medicine respectively, published 5 articles. Beginning with 1 article in the 1960's, 1 article in the 1970's, 4 articles in the 1980's, 13 articles in the 1990's, 34 articles in the 2000's and 6 articles from 2010 to 2012, the number of publications has been constantly increasing. Especially, clinical articles started to be published from 2000.

An overall review showed that the various effects of CCP recorded in medical classics were scientifically proven, though we suggest several opinions on the problems of this study.

Above all, the number of clinical studies is very insufficient compared to that of experimental studies, and the subjects are too weighted on musculoskeletal problems despite broad clinical coverage of CCP. Thus, more clinical studies should be focused on other kinds of diseases, such as, the endocrine system, the nervous system, gynecology, pediatrics, and so on. Secondly, in case of clinical studies, demonstrating the authentic clinical effects of CCP pharmacopuncture is difficult because many of them were combined with other therapies. Therefore, future case reports and RCTs should be solely designed with CCP pharmacopuncture. Thirdly, the method of syndrome differentiation (辨證) is not clearly stated, and clinical reproducibility is suspect. Diagnostic standards should be suggested for future studies. Lastly, although the safety of CCP pharmacopuncture has already been proven, CCP has a constitutional specificity from a Sasang typological point of view. Therefore, constitutional differences should be considered in further safety studies. Sincerely, we hope that this review will lead to better research and clinical applications in the future.

Various effects of CCP have been proven by many experimental studies; on the other hand, the number of clinical articles is insufficient. Through this review, more clinical studies seem to be necessary to substantially support the experimental effects of CCP. At present, it is a matter of fact that clinical trials of pharmacopuncture are limited due to inadequate pharmaceutical legislation; however, more aggressive research is needed on a variety of diseases within the possible bounds of the law.

This work was supported by a clinical research grant from Pusan National University Hospital 2013.

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