Paeonol (Pae), also known as peony phenol, is an active ingredient extracted from the dried root bark of the goldenseal family.

Modern studies have shown that paeonol has a wide range of pharmacological effects such as anti-inflammatory, anti-allergy, anti-oxidation, anti-tumor, etc. At present, it is mainly used for anti-thrombosis, anti-coronary atherosclerosis, ischemia reperfusion injury and so on.

1 Pharmacological Effects

1.1 Effects on the cardiovascular system

1.1.1 Anti-atherosclerosis

Sun Huiping established rat AS model by feeding high-fat diet and intraperitoneal injection of vitamin D3. The rats were randomly divided into normal group, model group, paeonol high-dose group and low-dose group. The levels of TNF-a and IL-6 were determined by ELISA. The expression of MCP-1 and ICAM-1 was detected by immunohistochemistry. The results showed that paeonol high dose group (20mg.kg') could improve the aortic lesions of AS rats, significantly reduce the levels of serum TNF-a and IL-6, and significantly down-regulate the expression of MCP-1 and ICAM-1 in aorta.

1.1.2 Myocardial infarction

Shi Shaoping4 used the left anterior descending coronary artery (LAD) ligation method to make the rat model of acute myocardial infarction in vivo. Based on the electrocardiogram evaluation, the rats with successful modeling were randomly divided into model group, paeonol low, medium and high dose groups, captopril group, and sham operation group without ligation. The heart mass index and infarct size of rats in each group were determined. Real-time fluorescence quantitative RT-qPCR was used to detect Smad2, Smad3 and Smad7mRNA expression levels in myocardial tissues of each group. The results showed that compared with model group, paeonol low, medium and high dose groups and captopril group significantly reduced myocardial infarction area and heart mass index. The mrna expression levels of Smad2 and SMAD3 in the model group were significantly higher than those in the sham operation group, and the expression of Smad7 was lower

In the sham operation group; The expression of Smad2 and Smad3mRNA in paeonol intervention group was significantly lower than that in model group, and the expression of Smad7mRNA was significantly stronger than that in model group.

1.1.3 Anti-ischemia-reperfusion injury

Lu Jianhong established a rat model of myocardial ischemia-reperfusion, and randomly divided 30 rats into sham operation group, model group and paeonol group. Each group was treated accordingly. Immunohistochemical method was used to detect the protein expression of Bel-2 and Bax in myocardial tissue, and Tunnel method was used to detect myocardial apoptosis. The results showed that the ratio of Bcl-2/Bax protein expression was increased in paeonol group, and the apoptosis rate of cardiomyocytes was significantly reduced. The mechanism is related to the regulation of apoptosis by the ratio of Bcl-2/Bax proteins.

1.2 Treatment of gastric ulcers

Zhang Xitong established a mouse model of ethanol-induced gastric ulcer, and randomly divided 60 mice into control group (given 0.9%Nacl injection), model group (given 0.9%Nacl injection), paeonol group (high, medium and low gavage doses of 200mg.kg-', 100mg.kg-', 50mg.kg'), and positive control group (positive control group). Ranitidine hydrochloride 40mg.kg-'), each administration group according to the dose of gavage

The drug was administered for 6 days. The results showed that with the increase of paeonol dose, the ulcer inhibition rate decreased significantly compared with the positive control group. The ulcer inhibition rate of low, medium and high doses of paeonol were 39.0%,58.5% and 82.9%, respectively. Therefore, paeonol has obvious protective effect on gastric mucosal injury caused by ethanol.

1.3 Treatment of skin tumors

Tao Yue used CCK8 to detect the proliferation inhibition rates of melanoma A375 and M14 cells. The cell cycle was measured by flow cytometry and the apoptosis rate of A375 and M14 cells after 24h treatment with paeonol was determined by Annexin-V/PE method. Hoechst33258 staining was used to observe the morphological changes of apoptosis in A375 and M14 cells treated with paeonol for 24h. The results showed that the G2/M phase cell cycle ratio of A375 and M14 cells treated with paeonol was higher than that of the control group, and the apoptosis of A375 and M14 cells was induced by the dose of paeonol. Therefore, paeonol can inhibit proliferation and induce apoptosis of melanoma A375 and M14 cells.

1.4 Treating Arthritis

Wu Qi used the anterior 1/3 of the medial meniscus of the knee joint and the anterior cruciate ligament to prepare the OA model. 1 week after treatment, a 2mm thick articular cartilage specimen of the articular surface of the medial condyle of the right femur was sliced and the structural changes in the chondrocytes were observed by transmission electron microscopy. The apoptosis index of chondrocytes was detected by TUNEL method. The expression of Bel-2 and Bax proteins in chondrocytes was determined by immunofluorescence method. The results showed that the apoptosis rate of the paeonol group decreased significantly compared with the control group

Phenol can significantly up-regulate the ratio of Bcl-2/Bax (P<0.01), inhibit apoptosis, and delay the degeneration and destruction of articular cartilage.

1.5 Treating Diabetes

Type 2 diabetic rat model was prepared by streptozotocin combined with high-fat diet. The diabetic rats were given different doses of paeonol by gavage for 40 consecutive days. Westhern Blotting and RT-PCR were used to detect the effects of paeonol on the expression of PPARy, GLP-1,PDX-1 and JNK1 proteins and genes in the pancreatic tissues of diabetic rats. The results showed that compared with the model group, the blood glucose of rats in both high-dose and low-dose groups decreased significantly, and the serum insulin also decreased significantly, which was close to the standard value of normal rats.

1.6 Treatment of acute liver cell injury

Yan Guiming established a model of elevated AST, ALT and MDA levels caused by alcohol-induced hepatocyte injury in rats. Different concentrations of paeonol (250, 125, 62.5, 31.25.15.625μmol/L) were incubated with acute injured liver cells for different times (0.5, 1, 3, 6, 12, 24h). The cell viability was determined by MTT colorimetric method, indicating the preventive effect of paeonol on liver injury ALT, AST and MDA levels of supernatant. The results showed that paeonol (125μmol/L,12h) significantly inhibited the effects of ethanol on hepatocyte injury, and paeonol group significantly reduced the release of ALT, AST and MDA levels in injured hepatocytes.

Clinical application:

1. Oral dosage form:

Paeonol tablets are composed of paeonol 20mg, medicinal talc 90mg, medicinal starch 90mg, and have certain curative effects on muscle pain, arthritis, toothache, stomach pain, abdominal pain and neuropathic pain. Weiyangping capsule is composed of paeonol 25mg, calcium carbonate 250mg, sodium carboxymethyl starch 20mg and 10% starch pulp, which is used for the treatment of chronic gastritis and gastric ulcer, the content of paeonol is 6128% and the dissolution rate is more than 70%.

2. Injection type

Paeonol has little water solubility, and increasing its solubility is the key to the process of making injection. At present, paeonol injection is the main clinical dosage form, which has been widely used in pain syndrome and dermatology clinic. 5% Xu Changqing injection is used for rheumatic pain, stomach pain and other pain, or for skin itching, atopic dermatitis, eczema and palma. Shi Yongxin treated 7 cases of cholinergic urticaria with paeonol injection (2ml each, containing 10mg paeonol) injected into Xuehai point (2ml on each side). After an average treatment of 715d, 6 cases were cured and 1 case had obvious effect. Yang Chunmei et al. applied paeonol injection (2ml each, including paeonol 10mg) into muscle and combined with symptomatic external drugs to treat 122 cases of eczema, pruritus and urticaria, and the efficacy was satisfactory.

3. Traditional topical dosage forms

Epaeonol ointment is made of epaeonol and clove oil. It is used for various skin diseases such as eczema, dermatitis, pruritus and so on. Paeonol oral film is mainly composed of paeonol, tween-80, glycyrrhizin monoamine salt and membrane adhesion matrix - vinyl alcohol. It has the advantages of good uniformity, stable content and direct absorption through oral mucosa. Using paeonol as the main raw material, analgesic and detumescence plaster can effectively inhibit acute inflammation and subacute inflammation (sarcodontia) in experimental rats, and its anti-inflammatory effect shows in the first hour after inflammation, which is a good anti-inflammatory topical drug.

4. New external dosage forms

Paeonol WPOPW double emulsion gel can be a new dosage form for clinical treatment of dermatosis. Paeonol phospholipid complex (molar ratio 1:1) can make paeonol embedded in lipid bilayer small body, easy to penetrate the skin stratum corneum, so as to achieve the purpose of transdermal.

The cumulative transdermal absorption rate of paeonol was lower than that of paeonol alone, indicating that paeonol phospholipid complex can not only penetrate the skin of isolated mice, but also has a sustained release effect on paeonol, suggesting that paeonol can be used in chronic diseases. This may be related to the large oil-water partition coefficient of its phospholipid complex, which can enter the stratum corneum quickly, and then store in the hydrophilic active epidermis and release slowly. In fact, only paeonol-B-cyclodextrin, paeonol-WPOPW emulsion and paeonol-phospholipid complex can be used not only for transdermal absorption dosage forms, but also for injection and oral dosage forms reform, expanding the administration of paeonol.

In SUMMARY:

In the treatment of traditional Chinese medicine, paeonol plaster has obvious curative effect on acute skin eczema and dermatitis. In addition, clinical trials have shown that it can inhibit the increase of capillary permeability, so it also has the effect of reducing inflammation and swelling. At the same time, paeonol has a good sedative effect on muscle tissue and skin, and can be used as a supplement for oral allergy and analgesic drugs instead of hormones, while its unique natural cooling fragrance can also help eliminate bad breath.

In addition, paeonol can also directly inhibit tyrosinase activity, melanin production and melanin transport, and its mechanism is multi-fold. Paeonol is used in the preparation of cosmetics or drugs for skin whitening and treatment of pigmentation diseases, which can achieve whitening effect and has a clear effect in the treatment of pigmentation diseases.