A New Strategy for Deleting Animal drugs from Traditional Chinese Medicines based on Modified Yimusake Formula

Abstract

Traditional Chinese medicine (TCM), such as Uyghur Medicine (UM) has been used in clinical treatment for many years. TCM is featured as multiple targets and complex mechanisms of action, which is normally a combination of medicinal herbs and sometimes even contains certain rare animal medicinal ingredients. A question arises as to whether these animal materials can be removed replaced from TCM applications due to their valuable rare resources or animal ethics. Here, we select a classical UM Yimusake formula, which contains 3 animal drugs and other 8 herbs, and has got wealthy experience and remarkable achievements in treating erectile dysfunction (ED) in China. The active components, drug targets and therapeutic mechanisms have been comprehensively analyzed by systemspharmacology methods. Additionally, to validate the inhibitory effects of all candidate compounds on their related targets, in vitro experiments, computational analysis and molecular dynamics simulations were performed. The results show that the modified, original and three animal materials display very similar mechanisms for an effective treatment of ED, indicating that it is quite possible to remove these three animal drugs from the original formula while still keep its efficiency. This work provides a new attempt for deleting animal materials from TCM, which should be important for optimization of traditional medicines.Traditional Chinese medicine (TCM) including Uyghur Medicine (UM) has been used for pharmaceutical and dietary therapy for several millennia 1 . UM is also characterized as multiple chemical components and multiple targets, which has been acknowledged with remarkable curative effects in treating some complex diseases such as arthritis, rheumatism, chronic back leg pain 2 . Due to these extensive use and the remarkable therapeutic effects, the interest in studying UM is gradually increased nowadays.However, UM often contains not only, as usual as common TCMs, a combination of many medicinal herbs, but also certain animal medicinal materials 3 . Some of these animal taxa like rhino, tiger, or musk beer, etc., are now at the brim of extinction due to commercial overexploitation 4 . Additionally, poaching of animals for their medicinal uses has also brought many wild species under the red data book, for a possibility of their extinction. For instance, bear bile has a decades-long history in the treatment of hepatic and biliary disorders, but it is just due to this extensive consumption of bear bile that has made bears become endangered species 5 . Moreover, the rapid deterioration of the natural biodiversity, as well as the loss and destruction of the habitat have also caused many rare animals in danger of extinction 4 . Due to these reasons, animal species for therapeutic purposes are becoming more and more precious, a question of whether animal ingredients in UM preparations can be removed arises, due to the current limitations of experimental approaches and the complex function mechanism of "multiple components, multiple targets" of...

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