August 14, 2024 longcha9

Research on the medication rules and related pharmacological analysis of ancient formulas for treating ankylosing spondylitis based on data mining and network pharmacology
Ankylosing spondylitis (AS) is an immune-mediated chronic inflammatory disease that mainly affects the axial and bilateral sacroiliac joints. It mainly affects the sacroiliac joint, hip joint, spinal ligament complex, and axial bone, causing pain, bone and joint destruction, stiffness, and ultimately leading to limited joint movement and stiffness and deformity. The main clinical manifestations are pain in the waist, back, neck, buttocks, and hips. In severe cases, spinal deformities and joint stiffness may occur, seriously affecting the quality of life of patients. At present, the incidence rate of AS is increasing year by year. This disease was first described by Marie. It is reported that the prevalence of AS in China is 0.22%. There is still no clear conclusion on its etiology, and genetic factors are closely related to AS. About 90% of AS patients have a relationship with genetic markers such as human leukocyte antigen B27 (HLAB27). Ruan et al. found that genetic polymorphisms of IL-12B (rs6871626) and IL-6R (rs4129267) are associated with increased risk of AS and can also serve as biomarkers for diagnosis and prognosis. In clinical practice, the treatment of AS mainly adopts comprehensive conservative treatment, and the preferred treatment drug for AS is nonsteroidal anti-inflammatory drugs. However, with the development of biologics, tumor necrosis factor – α (TNF – α) inhibitors have provided a new treatment method for AS patients who are ineffective or intolerant to NSAIDs. TNF – α is one of the cytokines that is closely associated with the pathogenesis of AS, and plays an important role in monitoring and clinical diagnosis of AS during its active phase. It has been confirmed that the TNF signaling pathway also plays an important role in the pathogenesis of AS. Specific inhibitors of TNF – α have also been widely used in the treatment of AS patients in clinical practice, and have achieved good therapeutic effects. It has been proven that they can improve the inflammatory status of the spine and sacroiliac joints. From ancient times to the present, traditional Chinese medicine experts have been committed to the unremitting pursuit of AS treatment. Traditional Chinese medicine has unique advantages in AS treatment, improving AS symptoms, and enhancing long-term efficacy. By consulting ancient medical books, it was found that there were many prescriptions used by ancient doctors to treat AS disease, but mainly based on individual syndrome differentiation and treatment. Modern medical research lacks exploration and analysis of the compatibility rules of ancient doctors’ prescriptions for treating AS disease. Therefore, the author adopts data mining technology, relying on modern computer and database technology, to discover patterns and models of data in large datasets, discover knowledge from the data, rely on massive network databases and computer information processing, analyze the collected ancient formula data, study the correlation between ancient formulas and summarize their formula compatibility rules, and explore the medication experience of ancient doctors in treating AS disease. Simultaneously applying modern network pharmacology techniques to analyze high-frequency drug combinations, further elucidating the modern pharmacological mechanisms of traditional Chinese medicine in treating AS from a molecular perspective, and providing certain clinical reference value for the clinical treatment of AS diseases with traditional Chinese medicine and the development of new formulas.

There is no such name as “ankylosing spondylitis” in ancient medical books. Ancient doctors classified ankylosing spondylitis as “bi syndrome”, “low back pain”, “bone bi” and other symptoms based on the patient’s poor flexion and extension of limbs, pain, and stiffness in the lower back. Modern renowned medical expert Professor Jiao Shude referred to this disease as “Dajian” and proposed that the etiology and pathogenesis of this disease are due to the combination of internal and external pathogens. The internal cause is kidney meridian yang deficiency, and the external cause is invasion of wind cold dampness, ultimately leading to the entry of external pathogens and damage to muscles and bones. Ma et al. believed that AS is mainly caused by diseases in the kidney meridian, where the kidney stores essence and the main bone generates marrow. The deficiency of yin and yang qi in the kidney cannot warm the tendons and meridians, resulting in strong and weak spines. This shows that the rise and fall of kidney essence is closely related to the strength and growth of bones. Throughout modern medicine, it is generally believed that in the early stages, this disease is mainly caused by pathogenic factors such as wind, cold, and dampness. Over time, phlegm and blood stasis accumulate, blocking the Du meridian. In the later stages, liver and kidney deficiency, as well as Du meridian deficiency, are the main causes, which can be summarized as “early pathogenic factors, middle blood stasis, and late deficiency”. Traditional Chinese medicine is a treasure of Chinese civilization with a long history of inheritance. There are countless medical literature and ancient books. With the development of information technology, online databases have provided us with convenience for researching and excavating ancient books. Especially the prescriptions in ancient books are the embodiment of ancient medical practitioners’ syndrome differentiation and treatment, and the summary of diagnosis and treatment experience. Through the analysis of Chinese herbs in ancient books, not only can the prescription and medication rules of traditional Chinese medicine for treating a certain disease be discovered, but also the etiology and pathogenesis of the disease can be inferred through the four qi and five wei, meridian tropism, and efficacy of traditional Chinese medicine. The first part of this article mainly summarizes, organizes and analyzes the prescriptions for treating AS in ancient medical books through the combination of network databases and modern computer technology. After sorting out 179 ancient prescriptions and analyzing 205 traditional Chinese medicines, it was found that ancient medical practitioners had a similar understanding of the etiology and pathogenesis of AS as modern medical practitioners. They believed that AS was mainly caused by the combination of internal and external pathogens due to the deficiency of the root and excess of the body. In terms of treatment and medication, they mainly used deficiency tonifying drugs, blood activating and stasis removing drugs, heat clearing drugs, exterior resolving drugs, and wind and dampness dispelling drugs, such as Eucommia ulmoides for liver and kidney strengthening muscles and bones, Achyranthes bidentata and Angelica sinensis for promoting blood circulation and removing blood stasis, clearing blood stasis and meridians, Duhuo, windbreak and dispelling wind and dampness. The four qi and five flavors of traditional Chinese medicine mainly consist of pungent, sweet, and bitter flavors, while the main medicinal properties are warm, calm, and cold. Xin can disperse and work effectively, warm and dispel cold and wind, Xin Wen can dispel surface cold and dispel dampness, allowing wind, cold, and dampness to dissipate from the surface; Ganping focuses on supplementing and strengthening the foundation; Bitter cold can clear heat, expel fire, and dry dampness. The meridian tropism is concentrated in the liver, kidney, spleen, and stomach meridians. AS mainly invades the joints and spine of the limbs, the liver controls the tendons, the kidneys control the bones, and the spleen and stomach are the foundation of postnatal development. If the spleen and stomach function normally and the liver and kidney essence and blood are sufficient, then the joint function of the limbs is normal.

Cluster analysis is an exploratory classification method that studies traditional Chinese medicine through an objective and scientific approach. The author conducted a systematic clustering analysis on traditional Chinese medicines with a usage frequency of ≥ 1%, and grouped them into 7 categories. Among them, kidney tonifying and bone strengthening drugs account for the majority. As AS is mainly caused by liver and kidney deficiency and damage to the Du meridian, deficiency tonifying drugs are often used to strengthen the body and consolidate the foundation. Secondly, there are drugs for promoting blood circulation and removing blood stasis, as well as drugs for clearing heat. Prolonged stagnation can lead to blood stasis and block the Du meridian, thus promoting blood circulation and removing blood stasis runs through the entire process. When blood stasis persists and turns into heat, heat clearing drugs are used to clear heat and relieve stagnation. In addition, surface clearing drugs and wind dampness removing drugs also play an important role in assisting the treatment of AS. “Wind is the strength of all diseases”, and the invasion of wind cold dampness external pathogens in AS is often related to wind pathogens. Therefore, surface clearing and dispelling cold, wind dispelling dampness, etc. Class I includes Windproof, Duhuo, Chuanxiong, Asarum, Gentiana, Cinnamomum cassia, Angelica sinensis, and Paeonia lactiflora. Windproof, Asarum, Gentiana, and Duhuo can dispel wind, relieve external symptoms, and relieve dampness and pain. Modern pharmacological studies have shown that Windproof and Asarum have antipyretic, anti-inflammatory, and analgesic effects; Class II includes Poria cocos, Ginseng, Rehmannia glutinosa, Eucommia ulmoides, Achyranthes bidentata, and Panax notoginseng, mainly used as kidney tonifying and bone strengthening drugs, filling lean marrow drugs. Among them, Rehmannia glutinosa, Eucommia ulmoides, and Panax notoginseng also have the effect of preventing and delaying osteoporosis, and have certain therapeutic effects on the late stage of AS complicated with osteoporosis; Class III: Dioscorea opposita, Salvia miltiorrhiza, Astragalus membranaceus. Salvia miltiorrhiza promotes blood circulation, removes blood stasis, and clears meridians, while Astragalus membranaceus replenishes qi and generates blood. Qi is the leader of blood, and when qi flows, blood flows; Class IV: Licorice, Atractylodes macrocephala, Dried Ginger, and Aconitum. Licorice can relieve pain and relieve pain, while Dried Ginger and Aconitum can warm the body and dispel cold, warm the kidney yang, and drive away evil spirits; Class V: Rehmannia glutinosa, which can clear heat and produce saliva. Modern pharmacological studies have shown that it has the function of enhancing humoral and cellular immunity; Category VI: Ginger, Qianghuo, Qianghuo relieves surface coldness, relieves wind and dampness pain, and also has anti-inflammatory and analgesic effects; Class VII: Psoraleae, fennel, and Cistanche deserticola. Psoraleae warms the kidneys and helps with yang, while Cistanche deserticola nourishes kidney yang, benefits essence and blood, and warms and nourishes the innate essence.

In addition, according to the association rule method, 35 commonly used drug combinations were selected and analyzed. The results showed that these combinations were mainly composed of tonifying deficiency drugs, promoting blood circulation and removing blood stasis drugs, resolving exterior problems, and dispelling wind and dampness drugs, such as Duhuo Fangfeng (dispelling wind and dampness drugs resolving exterior problems), Danggui Cinnamon (tonifying deficiency drugs warming interior problems), Du Zhong Achyranthes (tonifying deficiency drugs promoting blood circulation and removing blood stasis drugs), etc., which can be compared with high-frequency traditional Chinese medicines ranked high, confirming the reliability of their data. In the factor analysis of traditional Chinese medicine, 9 common factors were extracted, including CF1: Eucommia ulmoides, Achyranthes Achyranthes, Poria cocos, Radix Bupleuri, and Gentiana macrophylla (tonifying deficiency medicine, promoting blood circulation and removing blood stasis medicine, diuresis and dampness eliminating medicine, dispelling wind and dampness medicine); CF2: Windproof and Duhuo (anti surface medicine, anti wind and dampness medicine); CF3: Fructus Psorale, Fennel, Cistanche deserticola (a tonic and warming herb); CF4: Angelica sinensis, Rehmannia glutinosa, Ginseng (a tonic for deficiency); CF5: Fuzi, Atractylodes macrocephala (warming and tonifying herbs); CF6: Polygonum multiflorum, Astragalus membranaceus, Danshen (a medicinal herb that promotes diuresis and dampness, replenishes deficiency, and promotes blood circulation and removes blood stasis); CF7: Ginger, Qianghuo (anti surface medicine); CF8: Rehmannia glutinosa (heat clearing medicine); CF9: Dried ginger (warming herb). The results of factor analysis and association rule analysis are roughly the same, thus verifying the reliability of the data.

The first part analyzed the prescription and medication rules of ancient doctors in treating AS through data mining techniques. Traditional Chinese medicine is an empirical medicine, and doctors diagnose and treat based on syndrome differentiation. Through accumulated diagnosis and treatment experience, traditional Chinese medicine is combined and applied, gradually understanding the four qi and five flavors, meridian tropism, and efficacy of traditional Chinese medicine. With the development of modern medicine and in-depth research on traditional Chinese medicine pharmacology, pharmacological research and analysis of traditional Chinese medicine can be conducted through modern science and technology. The second part of this article selects the most frequently used Duhuo Fangfeng herb in ancient books for treating AS, and applies multiple network databases to conduct network pharmacology analysis, further elaborating on the molecular mechanism of Duhuo Fangfeng in treating AS. Duhuo, as a commonly used wind and dampness dispelling medicine, has a wide range of clinical applications. Hongjing said, “One stem straight up, not swayed by the wind, so it is called Duhuo.” “Bielu” says, “Duhuo is used to treat various winds, and there is no long-lasting new gout in a hundred joints. Windproof is a commonly used medicine for relieving external symptoms, with the functions of dispelling external cold, dispelling wind, removing dampness, and relieving pain. The “Changsha Medicinal Explanation” states: “Promote meridians, eliminate dampness and lust, unblock joints, relieve pain, relax tendons and meridians, stretch and twist rapidly, activate limbs and joints, cause paralysis, reduce sweating and helmet sweating, cut off leakage and collapse.” The “Classic of Materia Medica” states: “The main cause is dizziness and pain, evil wind, wind evil, blindness and blindness, spreading throughout the body, bone joint pain and numbness, and restlessness. The combination of Duhuo and Fangfeng, Duhuo has a pungent fragrance that can dispel wind, overcome dampness, unblock meridians, and relieve rheumatism and pain; Windproof, hair growth and evacuation, dispelling wind and dampness, opening pores, and promoting blood circulation. The “Commentary on the Classic of Rites” states: “Duhuo disperses dampness to transform the wind, and when combined with windbreak, it disperses the wind; when windbreak and dispells dampness, it disperses the wind, and when combined with Duhuo, it helps to remove dampness.” The two medicines complement each other and complement each other.

This study found through TCMSP database analysis that the active ingredients wogonin and beta sitosterol in Duhuo Fangfeng medicine interact with multiple targets with high correlation, indicating that they may be key components in the treatment of AS with Duhuo Fangfeng and play an important role in pharmacological action. Research has shown that the administration of baicalein can significantly inhibit the increase of inflammatory response. It prevents cell apoptosis by increasing the distribution of proteins such as caspase-9 and caspase-3, and has anti-inflammatory, antioxidant, and anti apoptotic effects. β – sitosterol has immunomodulatory and antioxidant effects, reduces NO synthesis, inhibits IL-6 activity, suppresses tumor necrosis factor aggregation and release, and has various physiological effects such as anti-inflammatory and antioxidant. Duhuo Fangfeng medicine has anti-inflammatory and antioxidant effects on baicalein and β – sitosterol, inhibits cell apoptosis, and enhances the body’s immunity. It is likely to be a key component in the treatment of atherosclerosis. Each active ingredient of a drug acts on multiple targets. To further elucidate the relationship between its target genes, network analysis was conducted between the target genes and disease targets, and 17 core targets were selected, mainly including IL6, TNF, PTGS2, CXCL8, etc. Some studies have shown that IL-6 can stimulate the aggregation of inflammatory cells and accelerate the synthesis of inflammatory mediators; TNF factor has various biological activities. As an important inflammatory factor, it can induce IL-6 expression, trigger inflammatory cascade reactions, catalyze and amplify inflammatory reactions and toxic effects. At the same time, it directly acts on vascular endothelial cells, changes cell permeability, and causes cell damage; PTGS can participate in inflammatory response and is an important target of non steroidal anti-inflammatory drugs. The treatment of AS with this type of drug mainly reduces the production of PG by inhibiting cyclooxygenase activity, thereby inhibiting the secretion of inflammatory factors and playing anti-inflammatory and analgesic roles; CXCL8 is a pro-inflammatory factor that accelerates the inflammatory expression of chondrocytes in limb joints, leading to cell apoptosis and exacerbating the progression of atherosclerosis. Based on the above research analysis, IL6, TNF, PTGS2, and CXCL8 may be key targets for the treatment of AS with Duhuo Fangfeng. Meanwhile, these key targets are mainly enriched in the TNF signaling pathway, VEGF signaling pathway, TOLL like receptor signaling pathway, NF kB signaling pathway, and HIF-1 signaling pathway, and mainly participate in inflammatory response, cell response to lipopolysaccharide, positive regulation of nitric oxide biosynthesis, positive regulation of NF kB transcription factor activity, and angiogenesis processes. Related studies have shown that in the late stage of atherosclerosis, biochemical reactions occur in the body, and the produced glycosylated compounds can activate NF kB by binding to its receptors, thereby causing multiple gene expressions and a series of inflammatory reactions, damaging bone cell proteins and hindering bone repair. The HIF-1 signaling pathway is an important pathway in the vascular osteogenic coupling reaction, which regulates the expression of multiple bone and angiogenic genes in the body, promotes angiogenesis, and synergistically promotes bone regeneration. The TNF signaling pathway and TOLL like receptor signaling pathway have been extensively reported in literature, and they are closely related to inflammatory response, immune response, and osteoclast differentiation and activation. Therefore, through network pharmacology analysis, it can be seen that components such as baicalein and β – sitosterol in Duhuo Fangfeng may act on the TNF signaling pathway, NF kB signaling pathway, and HIF-1 signaling pathway through targets such as IL6, TNF, PTGS2, CXCL8, forming a multi-component, multi-target, and multi-channel therapeutic characteristic, thereby exerting a therapeutic effect on AS.

In summary, through the application of data mining technology and network pharmacology technology, the prescription and medication rules of ancient doctors for treating AS were summarized and analyzed. Furthermore, the molecular mechanism of high-frequency drugs on the treatment of AS with Duhuo Fangfeng was further studied and analyzed, intuitively verifying the characteristics of the multi-component, multi-target, and multi-channel treatment of AS with Duhuo Fangfeng. This also indirectly reveals the uniqueness of traditional Chinese medicine in treating diseases. However, there are also many shortcomings in the research, and the data has certain limitations. Although the core target of Duhuo Fangfeng in treating AS has been preliminarily predicted through network pharmacology technology, providing new research ideas for the treatment of AS, further verification is also needed to provide reference value for clinical treatment.

Breathing new life into chemistry.

Qingdao Address: No. 216 Tongchuan Road, Licang District, Qingdao.

Jinan Address:No. 1, North Section Of Gangxing 3rd Road, Jinan Area Of Shandong Pilot Free Trade Zone, China.

Factory Address: Shibu Development Zone, Changyi City, Weifang City.

Contact with us by phone or email.

Email: info@longchangchemical.com

 

Tel & WA: +8613256193735

Fill in the form and we will contact you ASAP!

Please enable JavaScript in your browser to complete this form.
Please fill in your company name and personal name.
We will contact you through the email address you filled in.
If you have additional questions, please fill them in here.
en_USEnglish