Undescribed sesquiterpenoids with NO production inhibitory activity from oleo-gum resin of Commiphora myrrha.

Six undescribed cadinane sesquiterpenoids (1-6), two undescribed guaiane sesquiterpenoids (7-8), and an undescribed germacrane sesquiterpenoid (9) were isolated from the oleo-gum resin of Commiphora myrrha. Their structures were determined by the analysis of 1D/2D NMR and HRESIMS data, as well as quantum chemical ECD and NMR calculations. All the sesquiterpenoids were evaluated for their NO production inhibitory activity in LPS-stimulated RAW 264.7 mouse monocyte-macrophages. The results revealed that commiphone A (1) and commipholide D (7) exhibited significant inhibitory effect on NO generation with IC50 values of 18.6 ± 2.0 and 37.5 ± 1.5 µM, respectively. Furthermore, 1 and 7 dose-dependently inhibited the mRNA expression of inflammatory cytokines IL-1ß, IL-6 and TNF-α induced by LPS in the RAW264.7 cells, indicating that 1 and 7 possess potent anti-inflammatory activity in vitro.

Inhibitory Effect of Sesquiterpenoid M36 from Myrrha on Growth of Human Hepatoma Cells / 中国实验方剂学杂志

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC50） value of M36 for 48 h was 5.03 μmol·L-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

Essential Oils of the Leaves of Epaltes australis Less. and Lindera myrrha (Lour.) Merr.: Chemical Composition, Antimicrobial, Anti-inflammatory, Tyrosinase Inhibitory, and Molecular Docking Studies.

Epaltes australis Less. has been traditionally used to treat fever and snake bites, whereas Lindera myrrha (Lour.) Merr. is well-known for addressing colds, chest pain, indigestion, and worm infestations. This study marks the first report on the chemical compositions and biological potentials of essential oils extracted from the leaves of Epaltes australis and Lindera myrrha. Essential oils obtained by hydro-distillation were analysed using the GC/MS (gas chromatography-mass spectrometry). E. australis exhibited a predominant presence of non-terpenic compounds (46.3 %), with thymohydroquinone dimethyl ether as the major compound, constituting 44.2 % of the oil. L. myrrha leaf oil contained a good proportion of sesquiterpene hydrocarbons (56.8 %), with principal compounds including (E)-caryophyllene (22.2 %), ledene (9.7 %), selina-1,3,7(11)-trien-8-one (9.6 %), and α-pinene (7.0 %). Both essential oils exhibited antimicrobial activity against the bacteria Bacillus subtilis and Clostridium sporogenes, and Escherichia coli, and the fungus Aspergillus brasiliensis. L. myrrha leaf essential oil exhibited potent control over the yeast Saccharomyces cerevisiae with a MIC of 32 µg/mL. Additionally, L. myrrha leaf oil showed strong anti-inflammatory activity with an IC50 value of 15.20 µg/mL by inhibiting NO (nitric oxide) production in LPS (lipopolysaccharide)-stimulated RAW2647 murine macrophage cells. Regarding anti-tyrosinase activity, E. australis leaf oil showed the best monophenolase inhibition with the IC50 of 245.59 µg/mL, while L. myrrha leaf oil successfully inhibited diphenolase with the IC50 of 152.88 µg/mL. From molecular docking study, selina-1,3,7(11)-trien-8-one showed the highest affinity for both COX-2 (cyclooxygenase-2) and TNF-α (tumor necrosis factor-α) receptors. Hydrophobic interactions play a great role in the bindings of ligand-receptor complexes.

A new benzofuran compound from the resinous exudates of Commiphora myrrha.

A new benzofuran derivative, identified as myrrhain A (1), was isolated from the resinous exudates of Commiphora myrrha, together with the four known compounds: commipharane (2), myrrhterpeniod (3), myrrhone (4), and 9-methoxymyrrhone (5). All structures were elucidated by NMR and MS analyses. DPPH assay of compounds 1-5 revealed for the first time that all of them possess moderate antioxidative activity.

Professor ZHANG Boli's Experience in Treating Stubborn Bi （痹） with Ruxiang （Olibanum）-Moyao （Myrrha） Pair / 中医杂志

This paper summarized professor ZHANG Boli's experience in treating stubborn bi （痹） with the herbal pair of Ruxiang （Olibanum）- Moyao （Myrrha）. The basic pathogenesis of stubborn bi is channel and collateral stasis and obstruction. Ruxiang and Moyao are thus used in mutual reinforcement to rectify qi and diffuse bi， activate blood and relieve pain， thereby removing static and obstructed qi and blood， unblocking the obstructed channels and colla-terals， which is especially suitable for stubborn bi caused by channel and collateral obstruction. In clinical practice， the herbal pair of Ruxiang-Moyao is used together with qi-moving and blood-activating medicinals to treat chest bi by expelling stasis and diffusing stagnation， dissipating cold and unblocking vessels. To treat long-term wither and weakness in late stage of stroke， the medicinals of boosting qi and invigorating blood， unblocking channels and venting collaterals can be added to the herbal pair so as to soothe and drain vessels and collaterals， harmonize and regulate qi and blood. Simiao Yongan Decoction （四妙勇安汤） can be integrated in the treatment of vessel bi by moving qi and dissolving stasis， and for the long-term stubborn vessel bi， integrated internal and external treatment is suggested by external use of Ruxiang-Moyao to vent bi with aromatics. Moreover， it is emphasized to use the herbal pair of Ruxiang-Moyao in accordance with indications and cautions.

Effect of Natural Commiphora myrrha Extract against Hepatotoxicity Induced by Alcohol Intake in Rat Model.

The oral intake of alcohol has become a widespread concern due to its high risk to body health. Therefore, our purpose in this study was to reveal the antioxidant efficacies of natural Commiphora myrrha on hepatotoxicity and oxidative stress induced by ethanol in adult male rats, especially because these were not adequately revealed by previous studies. We examined the impacts of C. myrrha in male Sprague Dawley rats orally treated with C. myrrha (500 mg/kg) alone or in combination with 40% ethanol (3 g/kg), daily for 30 days. The results showed that treatment with C. myrrha after the oral consumption of ethanol caused a reduction in serum liver function parameters (alanine transferases, aspartate transaminase, and total bilirubin), hepatic tumor markers (α-L-flucosidase and arginase), and hepatic lipid peroxidation indicator (thiobarbituric acid reactive substances), as well as a slight restoration (not significant) in the levels of superoxide dismutase, catalase, reduced glutathione; and total antioxidant capacity. In addition, it alleviated histopathological changes in the liver, as revealed by decreased areas of inflammatory infiltrate, milder necrosis, and noticeably reduced periportal fibrosis and hemorrhage. The therapeutic efficiency of C. myrrha could be due to its rich sesquiterpenoids content which possesses anti-inflammatory properties and ROS-scavenging activities. Our findings provide evidence that the attenuation of oxidative stress by C. myrrha enables hepatic tissue to suppress inflammatory and oxidative mechanisms, resulting in enhanced liver structure and function. Therefore, C. myrrha extract shows promise as a protective and therapeutic supplement against toxic agents.

Cytotoxic sesquiterpenoid dimers from the resin of Commiphora myrrha Engl.

Seven undescribed sesquiterpenoid dimers, commiphomyrones A - G, together with three known analogs, were isolated from the resin of Commiphora myrrha Engl.. The structures of the undescribed compounds were elucidated based on a comprehensive analysis of spectroscopic data (NMR, UV, IR, and MS), and the absolute configurations were defined by comparing the experimental and calculated ECD spectra as well as by performing X-ray crystallographic analysis. All the isolated dimeric sesquiterpenoids feature a 7-oxabicyclo [2.2.1] hept-2-ene moiety formed by the [4 + 2] cycloaddition of two sesquiterpenoids. Commiphomyrones C and G and commiphoratone D showed cytotoxic activity against the HGC-27 cell line with IC50 values of 22.76, 25.01, and 27.51 µM, respectively.

In vitro cytogenotoxic and mutagenic effects of Commiphora myrrha essential oil.

Commiphora myrrha, located in the tropical zone, is a widely used tree for medicinal purposes in the Arabian Peninsula and a large part of Africa. In this research, cytogenotoxic effects of the commercially available Commiphora myrrha essential oil (myrrh) were studied using micronucleus (MN), comet, and total oxidant (TOS), and total antioxidant (TAS) assays on human peripheral lymphocytes under in vitro conditions. In addition, pure pBR322 plasmid DNA was used to investigate DNA damaging/protecting activity of the essential oil. Finally, a bacterial reversion (Ames) test was performed using Salmonella typhimurium mutant strains TA98 and TA100 to determine the potential effect of the agent in the induction of gene mutations. The high concentration of Commiphora myrrha (0.125 µL/mL) induced MN formation significantly compared to the untreated control in both treatment times (24 or 48 h). Only at the highest concentration, nuclear division index (NDI) values were found lower than the controls. In the Comet test performed on healthy lymphocytes, only the highest concentration of myrrh caused significant increases in the percentage of damaged cells and genetic damage index (GDI) values. Myrrh oil showed no significant mutagenic effect on mutant Salmonella strains. In addition, the substance did not directly damage plasmid DNA but also protected DNA against damaging factors such as H2O2 and UV. Finally, in the TAS and TOS assays, no significant differences on the oxidative stress parameters were found in cell culture compared to the control. The results of this study showed that myrrh oil exerts cytogenotoxic risk only at higher concentrations.

Herbal Textual Research on Myrrha in Famous Classical Formulas / 中国实验方剂学杂志

In order to provide the basis for the development of famous classical formulas containing Myrrha， the name， origin， quality evaluation， harvest and processing of Myrrha were systematically researched by consulting the ancient herbal and medical books， combining with the modern related literature. According to textual research， the results showed that Commiphora myrrha was the main base in ancient times， which was produced in Somalia， Ethiopia and northern Kenya. In addition， raw and fried products of Myrrha were the commonly used specifications in ancient herbal medicine， which are still used today. Nowadays， Myrrha， fried Myrrha and vinegar-processed Myrrha were the commonly used specifications. Among the three specifications， Myrrha is the raw products after cleaning， fried Myrrha is a kind of processed products， which has relevant records in ancient materia medica and is still used today. Vinegar-processed Myrrha is a new processing specification in modern times. Based on the research results， it is suggested that Myrrha in Shentong Zhuyutang should be the purified raw Myrrha in accordance with the 2020 edition of Chinese Pharmacopoeia.

Analysis of Olibanum and Myrrha by Differential Scanning Calorimetry and Fourier Transform InfraRed / 国际中医中药杂志

Objective:To distinguish the differences between Olibanum and Myrrha by using modern analytical methods such as Differential Scanning Calorimeter (DSC) and Fourier Transform InfraRed (FT-IR). Methods:By collecting Olibanum and Myrrha in different growing areas and different processed prosecures, this paper to analizes the influence of temperature increase and its speed , as well as the particle size on the DSC experiment. The DSC method was used to perform a differential thermal map of Olibanum and Myrrha scanning and analysis; FT-IR was used to scan and analyze 20 batches of Olibanum and Myrrha. Results:TThe results of DSC analysis showed that the DSC experimental condition ranged between 30-600 ℃; the speed of temperature increase was 30 ℃/min; the particle size was 100 mesh. The DSC spectra of of Olibanum and Myrrha were significantly different. Only the processed products of frankincense had endothermic peak near 297 ℃, and there was no characteristic peak in this temperature range. Their exothermic peaks are close at 326 ℃, but their enthalpy values are quite different. The position of endothermic peak near 100 ℃ is close to the size of peak shape. FT-IR test showed that the absorption peaks of Olibanum and Myrrha at wave numbers 2 925, 1 710, 1 454, 1 371, 1 242, 1 029 cm -1 appeared, and the positions of strong peaks were also similar. The intensity of the characteristic peak of Myrrha wave number 1 029 cm -1 is greater than that of Olibanum. Conclusion:The DSC spectra of Olibanum and Myrrha are significantly different, and the difference between the two FT-IR spectra is small. Differential scanning Calorimetry is an effective, fast, and simple way to identify resinous Chinese medicinal materials, and is worthy of further popularization.

[Ant i-inflammatory mechanism of active components in Olibanum and Myrrha based on network pharmacology and cell experiments].

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)-1ß 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.

Commiphora myrrha (Nees) Engl. resin extracts induce phase-I cytochrome P450 2C8, 2C9, 2C19, and 3A4 isoenzyme expressions in human hepatocellular carcinoma (HepG2) cells.

Commiphora myrrha (Nees) Engl. (C. myrrha) resin is the most Middle Eastern herbal medicine used against numerous diseases. After being decocted or macerated, this resin is widely consumed among Saudi Arabian patients who are already under prescribed medication. Despite its popularity, no studies have been reported on potential modulation effects of these resin extracts on drug metabolism. Therefore, we studied C. myrrha resin extracts on the expression of cytochrome P450 (CYP) drug-metabolizing isoenzyme in human hepatocellular carcinoma cell line HepG2. The C. myrrha extracts were prepared by sonication and boiling, resembling the most popular traditional preparations of maceration and decoction, respectively. Both boiled and sonicated aqueous extracts were fingerprinted using high-performance liquid chromatography equipped with ultra-violet detector (HPLC-UVD). The viability of HepG2 cells treated with these aqueous extracts was determined using CellTiter-Glo® assay in order to select the efficient and non-toxic resin extract concentrations for phase-I metabolic CYP isoenzyme expression analysis. The isoenzyme gene and protein expression levels of CYP 2C8, 2C9, 2C19, and 3A4 were assessed using reverse transcription-quantitative polymerase chain reaction and Western blot technologies. The HPLC-UVD fingerprinting revealed different chromatograms for C. myrrha boiled and sonicated aqueous extracts. Both aqueous extracts were toxic to HepG2 cells when tested at concentrations exceeding 150 µg/ml of the dry crude extract. The CYP 2C8, 2C9, and 2C19 mRNA expression levels increased up to 4.0-fold in HepG2 cells treated with either boiled or sonicated C. myrrha aqueous extracts tested between 1 and 30 µg/ml, as compared with the untreated cells. However, CYP3A4 mRNA expression level exceeded the 2.0-fold cutoff when the cells were exposed to 30 µg/ml of C. myrrha extracts. The up-regulation of CYP mRNA expression levels induced by both boiled and sonicated C. myrrha aqueous extracts was confirmed at the CYP protein expression levels. In conclusion, both sonicated and boiled C. myrrha aqueous extracts modulate CYP 2C8, 2C9, 2C19, and 3A4 gene expression at clinically-relevant concentrations regardless of preparation methods. Further in vitro and in vivo experiments are required for CYP isoenzyme activity assessment and the establishment of herb-drug interaction profile for these traditional medicinal resin extracts.

[Mechanism of Olibanum-Myrrha in treatment of rheumatoid arthritis based on network pharmacology and molecular docking].

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.

Investigation of Commiphora myrrha (Nees) Engl. Oil and Its Main Components for Antiviral Activity.

The resinous exudate produced by Commiphora myrrha (Nees) Engl. is commonly known as true myrrh and has been used since antiquity for several medicinal applications. Hundreds of metabolites have been identified in the volatile component of myrrh so far, mainly sesquiterpenes. Although several efforts have been devoted to identifying these sesquiterpenes, the phytochemical analyses have been performed by gas-chromatography/mass spectrometry (GC-MS) where the high temperature employed can promote degradation of the components. In this work, we report the extraction of C. myrrha by supercritical CO2, an extraction method known for the mild extraction conditions that allow avoiding undesired chemical reactions during the process. In addition, the analyses of myrrh oil and of its metabolites were performed by HPLC and GC-MS. Moreover, we evaluated the antiviral activity against influenza A virus of the myrrh extracts, that was possible to appreciate after the addition of vitamin E acetate (α-tocopheryl acetate) to the extract. Further, the single main bioactive components of the oil of C. myrrha commercially available were tested. Interestingly, we found that both furanodienone and curzerene affect viral replication by acting on different steps of the virus life cycle.

Lindermyrrhin, a novel 3,4-dihydroisocoumarin from Lindera myrrha roots.

A novel 3,4-dihydroisocoumarin, lindermyrrhin (1), along with three known compounds, quercetin (2), northalifoline (3) and N-formyl-laurolitsine (4) were isolated from the roots of Lindera myrrha. The structure of compound 1 was identified by interpretation of their spectroscopic data as well as comparison with those reported in the literature. The novel compound 1 represents the first 3,4-dihydroisocoumarin bearing a 2-hydroxyisopropyl substituent at C-3.

Mechanism of Olibanum-Myrrha in treatment of rheumatoid arthritis based on network pharmacology and molecular docking / 中国中药杂志

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.

A new cadinane-type sesquiterpenoid from Commiphora myrrha / 药学学报

Five cadinane-type sesquiterpenoids were isolated from the n-hexane extract of Commiphora myrrha by using various chromatographic techniques, including silica gel, ODS and semi-preparative HPLC. Their structures were identified by physicochemical properties and spectroscopic data. These compounds were defined as (3S,4R)-3,9-dimethoxymyrrhone (1), 9-methoxymyrrhone (2), myrrhone (3), commiterpene B (4) and comosone Ⅱ (5). Compound 1 is a new compound, of which the absolute configuration was established by single crystal X-ray crystallographic analysis. Compound 5 is firstly isolated from the Commiphora genus.

Ant i-inflammatory mechanism of active components in Olibanum and Myrrha based on network pharmacology and cell experiments / 中国中药杂志

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.

Commiphora Extract Mixture Ameliorates Monosodium Iodoacetate-Induced Osteoarthritis.

Osteoarthritis (OA) is a chronic inflammatory joint disease that affects millions of elderly people around the world. The conventional treatments for OA consisting of nonsteroidal anti-inflammatory drugs and steroid have negative health consequences, such as gastrointestinal, renal, and cardiac diseases. This study has evaluated the Commiphora extract mixture (HT083) on OA progression as an alternative treatment in animal models. The root of P. lactiflora and the gum resin of C. myrrha have been in use as traditional medicines against many health problems including bone disorders since ancient time. The extracts of P. lactiflora root and C. myrrha gum resin were mixed as 3:1 for their optimal effects. Male Sprague-Dawley rats were injected with monosodium iodoacetate (MIA) into the knee joints to induce the symptoms identical to human OA. HT083 substantially prevented the loss of weight-bearing inflicted with MIA in rats. The MIA-induced cartilage erosion as well as the subchondral bone damage in the rats was also reversed. In addition, the increase of serum IL-1ß concentration, a crucial pro-inflammatory cytokine involved in OA progression was countered by HT083. Furthermore, HT083 significantly reduced the acetic acid-induced writhing response in mice. In vitro, HT083 has shown potent anti-inflammatory activities by inhibiting the production of NO and suppressing the interleukin -1ß, interleukin -6, cyclooxygenase-2, and inducible nitric oxide synthase expression in lipopolysaccharide -stimulated RAW 264.7 cells. Given its potent analgesic and anti-inflammatory activities in MIA rats and acetic acid-induced writhing in mice, HT083 should be further studied in order to explain its mechanism of actions in alleviating OA pain and inflammation.

Efficacy and safety of myrrh in patients with incomplete abortion: a randomized, double-blind, placebo-controlled clinical study.

BACKGROUND: Myrrh (Commiphora myrrha (Nees) Engl.) has a long history of traditional use as a herbal medicine for different purposes. In ancient traditional Persian manuscripts, it has been noted that myrrh may act as uterine stimulant and probably cause complete abortion. However, there is no evidence to verify this comment. Therefore, the current study was carried out to evaluate the efficacy and safety of Myrrh in the treatment of incomplete abortion. MATERIALS AND METHODS: In a randomized double-blinded placebo controlled clinical trial, 80 patients with ultrasound-documented retained products of conception (RPOC) were assigned to receive capsules containing 500 mg of Myrrh oleo-gum-resin or a placebo three times a day for 2 weeks. The existence of the retained tissue and its size were evaluated by ultrasound examination at the beginning and end of the study. RESULTS: After 2 weeks, the mean diameter of the RPOC in the Myrrh group was significantly reduced compared with the placebo group (P < 0.001). Meanwhile, the rate of successful complete abortion was 82.9% in the intervention group and 54.3% in the placebo group (P = 0.01). The patients in both groups reported no serious drug-related adverse effects. CONCLUSION: This study shows that Myrrh is effective and safe in the resolution of the RPOC and may be considered as an alternative option for treatment of patients with incomplete abortion. However, further studies on active compounds isolated from myrrh and their uterine stimulant effects are needed. TRIAL REGISTRATION: This study was retrospectively registered at Iranian Registry of Clinical Trials (www.irct.ir) IRCT code: IRCT20140317017034N7.