Is “Pangolin (Manis Squama) is not used in medicine" an improvement in the protection of precious and rare species or an improvement in the safety of using medicine?

Bao-Tong Li, Yi Zhou, Xiao-Juan Su, Xiang-Long Meng *

NEWS

Is “Pangolin () is not used in medicine" an improvement in the protection of precious and rare species or an improvement in the safety of using medicine?

Bao-Tong Li2 #, Yi Zhou3 #, Xiao-Juan Su1, Xiang-Long Meng1 *

1Shanxi University of Chinese Medicine, Jinzhong 030619, China;2Guangxi University of Chinese Medicine, Nanning 530200, China;3The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410005, China.

Recently, a number of reports about pangolin have become hot news: The(2020 edition) has not continued to include the drug-using standards for pangolin (), aristolochic (), celestial vine (), and Chinese patent drug Huanglian Yanggan pills (approval number by China State Food and Drug Administration: Z200113194). On June 5, 2020, the China Forestry Administration Bureau and the Grassland Bureau co-issued an announcement to upgrade all the species of genus pangolins from the national second level of the protected wildlife to the first level. The new coronavirus (SARS-CoV-2) is also highly similar to the beta coronavirus isolated from pangolin [1]. For a time, “Pangolin is not used in medicine” triggered a hot topic of discussion among the public and the industry. The reason is that China is protecting the precious and rare species from the policy level? Or is it a delayed strategy in the safety of medication? It is worth pondering.

Pangolin is the essential medicine for “promote the secretion of milk protein and pain relief”

The pangolin is the pangolinbelonging to family Cyprinidae and genus pangolin. Its skin, stomach and blood can also be used as medicine. It was first recorded inpublished at the end of Han Dynasty (25 C.E.–220 C.E.)[2]. It is highly valuable animal medicinal material that has been widely used in internal, external, and gynecological clinics for promoting blood circulation and regulating menstruation. As many as 480 pangolin-related prescriptions have been used and recorded in ancient Chinese medical books and traditional Chinese medicine prescriptions [3].Additionally, modern pharmacology and clinical application studies have shown that it is mainly used for the treatment of analgesia [4], anti-inflammatory [5], carbuncle [6], rheumatoid arthritis [7] and other diseases as well.

Is the pangolin an intermediate host for SARS-CoV-2 from bat to human?

Since December 2019, a sudden outbreak of SARS-CoV-2 coronavirus [8] has caused a worldwide pandemic that has continued to date. Most coronaviruses originate from bats, such as SARS-CoV and MERS-CoV. However, their intermediate host(s) is/are still largely unclear. The pangolin carries a large number of parasites and viruses, and the positive rate of β-coronavirus is 70%. Further separation and identification of the virus revealed that the sequence identity between the isolated virus strain from the pangolin of main β-coronavirus and the current strain isolated from the infected humans is as high as 99% [9]. Liu et al. [10] revealed through genetic sequencing that the corresponding sequence identity between the genome fragments of pangolin virus derived from Malaysia and SARS-CoV- and SARS-CoV-like sequences is as high as 80% to 89%. Zheng et al. [11] analyzed pangolin samples collected by the customs of Guangdong and Guangxi in China and found novel coronaviruses representing two sublines related to SARS-CoV-2, but SARS-CoV-2 and their homology is about 85.5%–92.4%, which is lower than the homology (96.2%) of bat coronavirus (RaTG13). This does not appear to support the argument that pangolin is the intermediate host of SARS-CoV-2. However, for the coronavirus strains isolated by Xiao et al. [12] from the Malayan’s pangolin, the amino acid sequences of their E, M, N and S proteins are 100%, 98.6%, and 97.8% in homology with SARS-CoV-2, respectively, especially the receptor binding domain of pangolin coronavirus S protein is almost the same as that of SARS-CoV-2.This indicates that from the perspective of adapting to human cell receptors, pangolin appears to be consistent with the view of being an intermediate host for SARS-CoV-2. However, there is currently no further epidemiological evidence [13]. Therefore, whether the pangolin is the intermediate host for SARS-CoV-2 from bat to human still remains to be further verified.It is worth noting that the research report shows that pangolin meat may be the host of the new coronavirus. However, pangolin is not used directly as a raw piece of medicine in clinic, it only can be used as medicine after processing with high temperature as the pangolin scales [14]. Processing requires high temperatures, and the new coronavirus is not resistant to high temperatures. Thirty minutes at 56 °C will be enough to kill it. Therefore, it can be seen that pangolins can be safely used as medicine, and patients should not worry excessively about drug safety.

Do policies and regulations provide strong support for pangolin protection?

Pangolin prefers to inhabit in forests and shrubs in tropical and subtropical regions. It is mainly distributed in south of the Yangtze River, including Guangdong, Guangxi, Yunnan, Hainan and Taiwan provinces, in China, and is most commonly distributed in Guangxi [15–16]. However, since the 1970s, its population has been reduced by about 90% [17]. Illegal trade, destruction of its habitat, invasion of alien species, and its slow growth rate are the main threating factors. In order to further enhance the protection of pangolins, the Chinese government has discovered places where wild pangolins have been frequently present in recent years. The city Fangchenggang in Guangxi Province has set up a special national nature reserve in Shi-wan Mountains for protecting pangolin habitats. Thealso clearly states that illegal hunting, killing, transportation, and sale of a national-level protected animals can be regarded as “especially serious”, that is, imprisonment for more than ten years, and fines or confiscation of property. At the same time, approvals for artificial breeding and sale, purchase, and utilization of pangolins have also risen from the local to the national authorities. However, the specific implementation and actual benefits of policies and regulations will take time to verify.

Choice of alternative drugs for pangolin?

“Pangolin is not used in medicine”, does not deny its good medicinal value. However, how to find out a suitable alternative species, we also require rigorous scientific verification. Prior to this, there have been precedents for using the precious and rare substitutes or artificial breeding to solve such situations on the basis of ensuring the efficacy, such as buffalo horn replacing rhino horn, plug dragon bone replacing tiger bone, in vitro bezoar cultivation, and artificial cultivation of ginseng, etc. At the present, in terms of economic benefits and technical aspects, artificial breeding of pangolins is not feasible. However, there have been experiments to investigate the feasibility of the replacement of pangolin with pig’s toenail, and the results show that trotters have the same medicinal effect in the treatment of such diseases as inflammation, carbuncle, and impaired milk; Luo et al. [18] analyzed the differences in the chemical composition of between trotters and pangolins and they found that the chemical element types of the two were almost the same, and the types of amino acids were basically the same. Thus, there exists the feasibility of replacing pangolins with pig's toenail in the treatment of these diseases.

“Pangolin is not used in medicine” is a choice made out of many kinds of thinking

While the medicinal value of wild animals and plants cannot be ignored, they must also be protected from excessive hunting or exploitation and the safety of their medicines must be ensured. Due to large-scale consumer culture and habits and huge economic benefits, there are few pangolins in Asia. In January 2017, the Convention on International Trade in Endangered Species of Wild Fauna and Flora listed all eight species of pangolins in Appendix I, requiring that the commercial trade of pangolins be completely prohibited. Since then, any trade activities related to pangolins have been illegal. On the basis of the gradual improvement of laws and regulations, the state should strengthen popular science publicity activities, protect wild animals, and “resolutely prohibit wild animal markets and prohibit wild animal operations”. In the(2020 edition), the elimination of pangolins provides a good proof for the protection of medicinal wild animals. At the same time, how to explore the medicinal value of alternative medicines for precious and rare wild animals and plants and protect the ecological environment of their growth and habitat poses new challenges to us.

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Bao-Tong Li, Yi Zhou, Xiao-Juan Su, et al. Is “Pangolin () is not used in medicine” an improvement in the protection of precious and rare species or an improvement in the safety of using medicine? Traditional Medicine Research 2020, 5 (6): 425–427.

Xiang-Long Meng developed the idea for the study, coordinated and directed the article; Bao-Tong Li and Yi Zhou collected most of the data, drafted the manuscript; Xiao-Juan Su searched references, collated data.

The authors declare that they have no conflict of interest.

Rui-Wang Zhao.

15 July 2020.

1 September 2020.

06October 2020.

#Bao-Tong Li and Yi Zhou are co-first authors for this paper.

Xiang-Long Meng.College of Shanxi University of Chinese Medicine, No.121 University Street, Yuci District, Jinzhong 030619, China.E-mail: sszywzh@126.com.

10.12032/TMR20201001201