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BACKGROUND: “Ruxiang-Moyao” is a common combination of traditional Chinese medicine in the clinical treatment of knee osteoarthritis. However, the pharmacological mechanism is not yet clear. OBJECTIVE: Using network pharmacology technology to explore the therapeutic target of “Ruxiang-Moyao” as a commonly used traditional Chinese medicine for clinical treatment of arthromyodynia in the treatment of knee osteoarthritis and the relevant mechanism. METHODS: The chemical constituents of “Ruxiang-Moyao” were collected by TCMSP pharmacology database and analysis platform, and the possible bioactive constituents of frankincense and myrrh were screened according to the biological oral availability ≥ 30% and class drug properties ≥ 0.18. The possible targets of each active constituent were screened out using the protein database (Uniprot). GeneCards, OMIM, TTD and DrugBank databases were consulted to mine knee osteoarthritis-associated gene targets. The disease-drug protein target genes were obtained after the intersection of the above-mentioned screening data. The STRING database calculation and analysis algorithm was used to screen out important key genes to build a protein-protein interaction network, and the key target genes were uploaded to the PPI network graph. Cytoscape software was used to map the drug-target and disease-target visualization network, and DAVID online tool was further used for gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Gnomes (KEGG) pathway enrichment analysis. RESULTS AND CONCLUSION: Eight bioactive constituents of frankincense and 45 bioactive constituents of myrrh were obtained. At the same time, 412 target proteins of “Ruxiang-Moyao,” 1889 genes related to knee osteoarthritis and 105 co-targets of drugs and diseases were detected. The protein-protein interaction network found that AKT1, TP53, IL6, TNF, JUN, and MAPK1 might be the key targets of “Ruxiang-Moyao” in the treatment of knee osteoarthritis. The GO enrichment analysis identified 66 GO items, which are involved in cell response to hypoxia, negative regulation of epithelial cell proliferation, immune response, insulin-stimulated cell response, and positive regulation of fibroblast proliferation. The enrichment analysis of KEGG pathway identified 95 related signaling pathways, which are involved in inflammation, cell apoptosis and cell senescence. David enrichment analysis showed that the key target of “RuxiangMoyao” intervention for knee osteoarthritis was mainly related to several biological processes such as inflammatory response, cell apoptosis and immune system. Overall, “Ruxiang-Moyao” has the characteristics of multi-pathway and multi-target action in the treatment of knee osteoarthritis, and mainly has anti-inflammatory and analgesic effects. The key targets of its action and the involved biological process and signaling pathway have been preliminarily revealed, providing a new idea for the clinical prescription treatment of knee osteoarthritis in the future. [ABSTRACT FROM AUTHOR]

This study first optimized the processing technology for Zhangbang vinegar-processed Olibanum and investigated its in vitro anticoagulant activity. A multi-index-response surface methodology was used, with yield, powder yield, and the relative percentage of the content of six non-volatile components [11-keto-boswellic acid(KBA), 3-acetyl-11-keto-boswellic acid(AKBA), β-elemonic acid, α-boswellic acid(α-BA), β-boswellic acid(β-BA), and α-acetyl-boswellic acid(α-BA)] and three volatile components(octyl acetate, incensole, and incensole acetate) as evaluation indicators. Analytical hierarchy process(AHP) combined with coefficient of variation method was used to calculate the weight of each indicator and calculate the comprehensive score(OD). Furthermore, response surface methodology was used to investigate the effects of frying temperature(A), burning time(B), rice vinegar dosage(C), and steaming time(D) on the processing technology of vinegar-processed Olibanum. Vinegar-steamed Olibanum was prepared according to the optimal processing technology for in vitro anticoagulant experiments. The results showed that the weights of octyl acetate, incensole, incensole acetate, KBA, AKBA, β-elemonic acid, α-BA, β-BA, α-ABA, yield, and powder yield were 0.358 2, 0.104 5, 0.146 4, 0.032 9, 0.123 7, 0.044 4, 0.022 1, 0.042 2, 0.110 1, 0.012 2, and 0.0032, respectively. The optimal processing technology for Zhangbang vinegar-processed Olibanum was as follows. Olibanum(50 g) with a particle size of 1-5 mm was continuously stir-fried at a low heat of 150-180 ℃ until in a gel-like state, ignited for burning for 15 s, sprayed with 7.5 g of rice vinegar(15%), and steamed for 3 min without fire. Subsequently, the cover was removed, and the product was continuously stir-fried at 150-180 ℃ until in a soft lump shape, removed, cooled, and crushed. The results of the in vitro anticoagulant experiments showed that compared with the blank group, both Olibanum and vinegar-processed Olibanum significantly prolonged the activated partial thromboplastin time(APTT), thrombin time(TT), and prothrombin time(PT) of rat platelet-poor plasma(PPP), and the effect of vinegar-processed Olibanum was significantly better than that of Olibanum(P<0.05). The optimized processing technology for Zhangbang vinegar-processed Olibanum is stable, feasible, and beneficial for the further development and utilization of Olibanum slices. At the same time, using the content of volatile and non-volatile components, yield, and powder yield as indicators, and verifying through pharmacological experiments, the obtained results are more reasonable and credible, and have positive guiding significance for the clinical application of characteristic processed Olibanum products.

The present study collected data on traditional Chinese medicine(TCM) compounds effective in relieving pain from the patent database of the State Intellectual Property Office(SIPO), sorted out the TCM compounds against pain in patents, and analyzed the medication rules to provide references for the research and development of new TCM drugs against pain. The data were subjected to frequency statistics, association rules, cluster analysis, and complex network analysis by IBM SPSS Modeler 18.3 and SPSS Statistical 26.0. The results showed that among the 101 oral prescriptions included in the statistics, the top 5 drugs were Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, Chuanxiong Rhizoma, and Salviae Miltiorrhizae Radix et Rhizoma, and among the 49 external prescriptions included in the statistics, the top 5 drugs were Myrrha, Olibanum, Angelicae Dahuricae Radix, Borneolum Syntheticum, and Chuanxiong Rhizoma. Whether oral or external prescriptions, the drugs were mainly warm in nature, and bitter, pungent, and sweet in flavor. According to TCM complex network analysis, the core drugs were Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, and Chuanxiong Rhizoma in oral prescriptions, and Olibanum, Myrrha, Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Angelicae Sinensis Radix in external prescriptions. Overall, the therapeutic principles of oral prescriptions were mainly replenishing Qi, nourishing blood, and promoting Qi and blood circulation, while those of external prescriptions were activating blood, resolving stasis, promoting Qi flow, and relieving pain on the basis of the oral prescriptions. In the future research and development of TCM compounds against pain, the prescriptions should be modified with mind-tranquilizing and depression-relieving drugs. With the modernization of TCM, the development of new pain-relieving TCM compound patents based on ancient methods and clinical experience adhering to the guidance of TCM treatment based on syndrome differentiation can meet the new demand for pain treatment in the current society and give full play to the advantages of TCM in pain treatment.

Herbal pair is formed based on the experience summary of doctors' deep understanding and perception of the medicinal nature in long-term clinical practice. It gradually becomes the exquisite structural unit for preparing traditional Chinese medicine(TCM) prescriptions, and often plays a core bridge role in the prescription combination. Frankincense and myrrh are raw resin materials of incense abroad, which are subsequently included as Chinese medicinal herbs and endowed with rich medicinal connotation. With the functions of relaxing Zang-fu organs, activating blood and relieving pain, they have definite clinical efficacy. From the perspective of herbal description and clinical application, this study systematically analyzed the combination of frankincense and myrrh as well as their combination proportion, efficacy characterization, diseases and syndromes, effective components and action mechanism. On this basis, the focus of in-depth research of frankincense-myrrh and the application prospects were proposed, in order to further reveal the potential meditation law of this herbal pair, thus contributing to clinical practice and drug innovation of traditional Chinese medicine, and providing reference for understanding of TCM medicinal nature and research of herbal pairs.

Five compounds were isolated from the alcohol extract of Olibanum by MCI, silica gel, ODS, and Sephadex LH-20 column chromatographies and preparative high-performance liquid chromatography(HPLC). On the basis of spectral data and literature data, the compounds were identified as:(1S,3R,4S,7R,11S,12R)-1:12,4:7-diepoxisonane-8(19)-ene-3,11-diol(1), boscartin A(2),(+)-resinolin(3),(+)-5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one(4), and acerogenin A(5). Compound 1 is a new compound, and compounds 3-5 were isolated from Olibanum for the first time. The structure of compound 1 was determined by spectroscopic analysis and single-crystal X-ray diffraction. Compounds 1 and 2 were tested for PC12 neurotoxicity, and the results showed that they were both safe compounds.

Two terpenes, 3-keto-tirucalla-8,24-dien-21-oic acid(KTDA) and 2-methoxy-5-acetoxy-furanogermacr-1(10)-en-6-one(FSA), are isolated from Olibanum and Myrrha respectively, which are characterized by high yield and easy crystallization during the preparation. The present study explored the regulatory targets and anti-inflammatory mechanism of KTDA and FSA based on network pharmacology and cell viability assay. First, the drug-likeness of KTDA and FSA was predicted by Swiss ADME. The target prediction of active components was carried out by Swiss Target Prediction and Pharmmapper. TTD, Drug Bank, and Gene Cards were searched for inflammation-related target genes of KTDA and FSA. Protein-protein interaction(PPI) analysis was performed on the inflammatory targets of KTDA and FSA by STRING, and Cytoscape was used to conduct topological analysis of the interaction results and construct the PPI network. GO function and KEGG pathway enrichment analyses of inflammatory targets of KTDA and FSA were carried out by DAVID, and a " component-target-pathway" network was constructed. Finally, lipopolysaccharide(LPS)-induced RAW264. 7 cells were treated with KTDA and FSA at different concentrations, and nitric oxide(NO) concentration and protein and m RNA expression levels were detected. The results showed that both KTDA and FSA showed good drug-likeness. A total of 157 and 142 inflammation-related targets of KTDA and FSA were screened out. PPI network analysis showed that MAPK1, AKT1, MAPK8, PIK3 CA,PIK3 R1, EGFR, etc. might be the key proteins for the anti-inflammatory effect. PI3 K/AKT and MAPK signaling pathways were obtained by KEGG and GO-BP enrichment. Cell experiment results showed that KTDA and FSA could exert anti-inflammatory effects by inhibiting NO production, reducing the phosphorylation levels of JNK, p38, and AKT proteins, and down-regulating the m RNA expression of interleukin(IL)-1β and IL-6. Meanwhile, FSA could also inhibit ERK phosphorylation. The results indicated that KTDA and FSA had significant anti-inflammatory activity, which provided a scientific basis and important support for the further research,development, and utilization of Olibanum and Myrrha.

In this paper, network pharmacology method and molecular docking technique were used to investigate the target genes of Olibanum and Myrrha compatibility and the possible mechanism of action in the treatment of rheumatoid arthritis(RA). Our team obtained the main active components of Olibanum-Myrrha based on literatures study, relevant traditional Chinese medicine systematic pharmacological databases and literature retrieval, and made target prediction of the active components through SwissTargetPrediction database. At the same time, RA-related targets were collected through DrugBank, GeneCards and Therapeutic Target Database(TDD) databases; and VENNY 2.1 was use to collect intersection targets to map common targets of drug and disease of Venn diagram online. The team used STRING database to construct PPI protein interaction network diagram, and screen out core targets according to the size of the interaction, and Cytoscape 3.6.0 software was used to construct network models of "traditional Chinese medicine-component-target" "traditional Chinese medicine-component-target-disease" and core target interaction network model. The intersection target was analyzed by using DAVID 6.8 online database for GO function analysis and KEGG pathway enrichment analysis, and Pathon was used to visualization. AutoDock Vina and Pymol were used to connect the core active components with the core targets. Sixteen active components of Olibanum-Myrrha pairs were found and collected in the laboratory, and 320 relevant potential targets, 468 RA-related targets and 62 intersection targets were obtained through the Venn diagram. It mainly acted on multiple targets, such as IL6, TNF, IL1 B and MAPK1, involving TNF signaling pathway and Toll-like receptor signaling pathway in RA treatment. Finally, in this study, possible targets and signaling pathways of Olibanum-Myrrha compatibility therapy for RA were discussed, and molecular docking between core targets and core active components was conducted, which could provide scientific basis for the study on the mechanism of Olibanum-Myrrha compatibility.

The volatile oil from Mastiche and Olibanum medicinal materials was extracted by steam distillation, and the chemical components of the volatile oil were analyzed by GC-MS technology. The differences of the volatile oil components were compared and study on the Helicobacter pylori in vitro antimicrobial activitiy was conducted. The results showed that the yields of the volatile oil from Mastiche and Olibanum were 11.93% and 2.40%, respectively. A total of 46 compounds(91.31%) were identified from the volatile oil from Mastiche annd 35 compounds(92.49%) from Olibanum. The classification and comparison study of the components showed that the content of monoterpenes in the volatile oil from Mastiche was the highest(40.69%), followed by alcohols(28.48%); while the content of alcohols in the volatile oil from Olibanum was the highest(35.81%), followed by esters(24.92%). There were significant differences in the components of volatile oil from Mastiche and Olibanum, which might be one of the reasons for the difference in efficacy and application. In vitro bacteriostatic experiments showed that the minimum inhibitory concentration(MIC) of the volatile oil from Mastiche against H. pylori was 1 mg·mL~(-1), and the MIC of the volatile oil from Olibanum against H. pylori was more than 1 mg·mL~(-1). In combination with the results of the oil yield experiment, Mastiche had the advantage of inhibiting H. pylori activity. The research results provide scientific basis for the rational application of Mastiche and Olibanum.

As a representative foreign medicinal material, olibanum(Ruxiang) was imported to China since the Qin and Han Dynasties. Olibanum was first described as a medicinal by the name "Xunluxiang" in Miscellaneous Records of Famous Physicians(Ming Yi Bie Lu). This study investigated historical records on olibanum and conducted the herbalogical study. It was found that olibanum came from the resin mainly obtained from the bark of Pistacia lenticus before the Tang Dynasty. With the prosperity of the Maritime Silk Road, instead, the resin obtained from the bark of Boswellia carterii was mainly used as olibanum. In ancient time, the oleo-gum-resin secreted from the cut bark was collected in spring and summer, and the quality was judged based on transparency and shape. The processing methods of olibanum went through many evolutions, which changed from simple methods such as grinding and frying to complex methods such as levigating and grinding with wine, and now to frying and processing with vinegar. The usage of olibanum included alchemy, folk and religious incense, bathing, cosmetic and medicinal since ancient times. From the Song Dynasty, olibanum had been mainly used as medicinal because of its good effect to treat wounds. In traditional Chinese medicine, olibanum unblocks menstruation, relieves pain and reduces swelling and generated muscles. The medicinal efficacy of olibanum is not much different from ancient to modern. Only the efficacy of replenishing energy and promoting the movement of Qi was rarely mentioned in modern reference. In this article, the historical evolutions of olibanum about original plants, processing and medicinal efficacy were sorted out. The results could provide historical basis for the further development and clinical utilization of olibanum.