Application and Prospect of Cold Hoop Confining Method in Psoriasis from Dermatopathology in Integrated Chinese and Western Medicine

Xinwen LI, Bin ZHANG, Qingchun DIAO, Xiangyu HU

Department of Dermatology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400000, China

Abstract In the pathological changes of psoriasis vulgaris, excessive proliferation of keratinocytes, proliferation of microvessels, infiltration of a large number of inflammatory cells, and great shortening of epidermal replacement time, are the manifestations of Qi and Yin depletion, and they all correspond with pathological changes of nutrient Qi and blood deficiency caused by excessive loss. The treatment of psoriasis should focus on cold straight fire, convergence and fixation. Therefore, it is feasible to treat psoriasis with hoop in theory, and it is found that "cold hoop confining medicine" may be more suitable for the treatment of psoriasis vulgaris in the gradual progress of the experiment. The research could provide theoretical basis for the application of cold hoop confining medicine represented by brusatol in psoriasis vulgaris and related diseases.

Key words Psoriasis vulgaris, Cold hoop confining method, Brusatol, Dermatopathology

1 Introduction

Psoriasis is a kind of immune mediated chronic, recurrent, inflammatory and systemic disease commonly induced by heredity and environment[1]. The records of TCM on this disease can be traced back to theOriginofVariousDiseases:Psoriasis, and it is recorded that "if psoriasis occurs, skin is dry and feels itching, and the white chip could be scratched out". In Japan, the disease is still called psoriasis.

2 Pathogenic mechanism

Traditional Chinese medicine believes that "the body is rich in blood heat, and the blood is deficient, so the skin is dystrophic, and feels dry", thereby generating psoriasis. According to the mainstream academic view, it is thought that heat is the main factor at the beginning, and then deficiency occurs after a long time, and stagnation occurs after a longer time. In the 2018ChineseGuidelinesfortheDiagnosisandTreatmentofPsoriasis, it clearly put forward that the latent evil in collaterals is the basis for the pathogenesis of psoriasis, and Qi stagnation and blood stasis are the initial pathogenesis of psoriasis, and stasis heat and blood toxin are the core pathogenesis of psoriasis. In psoriasis vulgaris, blood heat syndrome, blood dryness syndrome and blood stasis syndrome are the basic syndromes[1].

From the perspective of pathological keratinocyte proliferation, the disease belongs to the state of "scattered but not collected", and it is an effective way to clear away heat and cool the fire. Traditional external prescription of the disease mostly uses coptis ointment in theYizongJinjian. In 2014, experts proposed using external application of traditional Chinese medicine ointment for clearing away heat and toxin, moistening the skin, and relieving itching, dominant by appeasing, and avoiding irritation[2]. In the 2018ChineseGuidelinesfortheDiagnosisandTreatmentofPsoriasis, these external prescriptions are followed. A large number of pharmacology has confirmed that the mechanism of these antipyretic, detoxicating, and blood cooling drugs is to inhibit cell mitosis, promote the formation of granular layer, improve the keratinization of epidermis, and transform from incomplete keratinization to complete keratinization of granular layer[3-4]. However, in the pathological changes of psoriasis vulgaris, microvascular hyperplasia, inflammatory cell infiltration and excessive proliferation of keratinocytes are also prominent, and even the earliest[5]. To change microvascular proliferation and inflammatory cell infiltration, it is difficult to achieve the effect only through the application of traditional Chinese medicine ointment which can clear away heat and detoxify, moisten skin and relieve itching.

Traditional Chinese medicine believes that "where the evil is gathered, the Qi will be deficient", and "long illness will dissipate it". Additionally, it is also thought that "the body is rich in blood heat, and the blood is deficient", thereby causing disease. Deficiency is caused by many deficiencies and losses. During the progressive period, the blood heat is burnt, and the Qi is consumed, and the Yin is damaged. In the stable stage, the Yin blood is insufficient. The proliferation of keratinocytes, proliferation of microvessels, infiltration of a large number of inflammatory cells, and greatly shorting of epidermal replacement time, are all the causes of Qi and Yin depletion. Therefore, psoriasis should belong to deficiency of nutrient Qi and blood caused by excessive loss. The treatment of psoriasis should focus on cold straight fire, convergence and fixation.

Therefore, for psoriasis, is there a kind of external therapy or external Chinese medicine that can perfectly give consideration to both heat clearing and detoxification and have the effect of astringency and fixation?

3 Application and prospect of cold hoop confining method in psoriasis

In the external treatment method, it is mentioned that the hoop has the function of convergence and fixation. Since the drugs have different taste and meridian tropism, hoop is divided into cold hoop confining method, warming hoop and converging hoop. Zhu Renkang thinks that "hoop medicine is an external treatment method which applies drugs around the affected areas, to collect the sore shape and prevent the spread of toxicity and evil, and to make the sores easy to eliminate, break and collect"[6]. The method has long application history, and as early as "Yiyongjie" in theFormulasforFifty-TwoDiseases, there was a prescription for hoop medicines. In modern classicsLexiconofTraditionalChineseMedicine, it is clearly put forward that its functions are to cut off poison, bundle poison, extract poison, warm, remove blood stasis, clear away heat, settle pain and expel poison[7].

Under the guidance of the "hoop" theory, our team has done exploratory research on Wubeizi which is one of the representative convergence hoop medicine. By inducing animal models, it has been proved that the external use of Wubeizi can effectively improve the excessive keratinization of the epidermis of experimental animals, reduce the microvascular density per unit area of skin lesions, decline VEGF and NO in serum, and decrease the expression of IL-4 and Foxp3 in CD4+T cell of skin lesions[8-10]. However, there is lack of study on specific signaling pathway. Single traditional Chinese medicine is still a compound preparation with complex components. These results confirmed that the idea of hoop medicine in the treatment of psoriasis vulgaris is feasible, and "cold hoop confining medicine" may be more suitable for the treatment of psoriasis vulgaris. Cold hoop confining medicine has not only the function of clearing away heat and toxin, but also the function of converging and floating collaterals, reducing the flow of Qi and blood, making that the skin of excessive proliferation looses enough Qi and blood nourishment, not glory but withered, thereby magnifying the curative effect of clearing away, bundling poison, cutting poison and removing poison in the treatment of psoriasis. Out group studied brusatol (BR) which is representative monomeric drug of cold hoop confining medicine. Preliminary results have proved that BR could intervene proliferation promotion induced by TNF-α, and inhibit cell proliferation by mediating arrest of cell cycle. Additionally, it also could down regulate the expression of CRNN and CyclinD1, and intervene phosphorylation of Akt protein. Additionally, ELISA experimental results showed that BR could decline the expression of inflammatory factors IFN-γ and IL-17 secreted by splenic lymphocytes in mice, and inhibit inflammatory reaction induced or maintained by IFN-γ and IL-17, thereby effectively improving symptoms of psoriasis like model[11].

However, it remains to be confirmed whether BR can reduce the proliferation of blood vessels in plaque by down regulating IL-9/VEGF pathway to reach compound therapeutic effect. There is still a long way to go for the acceptance, application and clinical transformation of monomer drugs. Seen from current results, it is still verified that cold hoop confining medicine represented by BR has a great future in the application of psoriasis vulgaris. Moreover, for the diseases with similar pathological features, such as malignant melanoma, BR still shows excellent curative effect and application prospect in its diagnosis and treatment process and application of traditional Chinese Medicine under the guidance of the idea[12].