Evaluation of Comparative Efficacy of Levothyroxine Versus Kshar Basti and Kanchanar Guggul in the Treatment of Hypothyroidism: Protocol for a Randomized Controlled Trial.

BACKGROUND: The thyroid gland is an endocrine gland that has an impact on the body's general metabolism. Thus, the secretions of the thyroid gland can modify the overall metabolism of the entire body. The prevalence of hypothyroidism is increasing quickly, with rates of 2%-5% in affluent countries and 11% in India. Individuals diagnosed with hypothyroidism need to take medication for the rest of their lives, resulting in significant stress. Therefore, conducting a study in this area is imperative. OBJECTIVE: This study aims to assess the effectiveness of the therapeutic enema (Kshar Basti) and oral Kanchanar Guggul in the treatment of hypothyroidism. METHODS: The trial group (n=45) will receive a therapeutic enema (Kshar Basti) followed by oral Ayurvedic drugs for 180 days. The control group (n=45) will be given levothyroxine tablets at a dosage of 1.6 µg/kg/day for the same duration. The objective is to examine the alterations in thyroid stimulating hormone (TSH) levels before and after the treatment. RESULTS: Any deviation of the serum TSH by more than 20% from the initial values, while keeping triiodothyronine (T3), and thyroxine (T4) levels within the normal range, will be deemed statistically significant. Consequently, we anticipate a statistically significant variation in serum TSH levels between the therapeutic enema and Kanchanar Guggul treatments. Presently, the drug preparation operations are in progress. We expect to start enrolling patients in June 2024, do data analysis in December 2025, and acquire results by early 2026, marking the end of this trial. CONCLUSIONS: This study will evaluate the efficacy of the therapeutic enema, specifically Kshar Basti, in treating hypothyroidism. Furthermore, more research can determine the efficacy of a therapeutic enema (Kshar Basti) in treating overt hypothyroidism and hypothyroidism during pregnancy. TRIAL REGISTRATION: Clinical Trials Registry India CTRI/2023/05/052389; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=Nzk1NjY=&Enc=&userName=052389. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/57287.

An Unprecedented 4,8-Cycloeudesmane, Further New Sesquiterpenoids, a Triterpene, Steroids, and a Lignan from the Resin of Commiphora myrrha and Their Anti-Inflammatory Activity In Vitro.

Myrrh has a long tradition in the treatment of inflammatory diseases. However, many of its (active) constituents are still unknown. In the present study, secondary metabolites were isolated from an ethanolic extract by various separation methods (liquid-liquid partition, silica and RP18 flash chromatography, CPC, and preparative HPLC), their structures were elucidated with NMR spectroscopy and mass spectrometry, and the selected compounds were tested for their effect on LPS-induced NO production by RAW 264.7 murine macrophages. Among the isolated substances are 17 sesquiterpenes (1-17) including the first 4,8-cycloeudesmane (1), a triterpene (38), two phytosterols (39, 40) and one lignan (43), which were previously unknown as natural products. Numerous compounds are described for the first time for the genus Commiphora. Eight of the eleven compounds tested (1, 29, 31, 32, 34-37) showed a statistically significant, concentration-dependent weak to moderate anti-inflammatory effect on NO production in the LPS-stimulated RAW 264.7 macrophages in vitro. For the reference substance, furanoeudesma-1,3-diene, an IC50 of 46.0 µM was determined. These sesquiterpenes might therefore be part of the multi-target molecular principles behind the efficacy of myrrh in inflammatory diseases.

Characterization and analysis of a Commiphora species germinated from an ancient seed suggests a possible connection to a species mentioned in the Bible.

A seed recovered during archaeological excavations of a cave in the Judean desert was germinated, with radiocarbon analysis indicating an age of 993 CE- 1202 calCE. DNA sequencing and phylogenetic analysis identified the seedling as belonging to the angiosperm genus Commiphora Jacq., sister to three Southern African Commiphora species, but unique from all other species sampled to date. The germinated seedling was not closely related to Commiphora species commonly harvested for their fragrant oleoresins including Commiphora gileadensis (L.) C.Chr., candidate for the locally extinct "Judean Balsam" or "Balm of Gilead" of antiquity. GC-MS analysis revealed minimal fragrant compounds but abundance of those associated with multi-target bioactivity and a previously undescribed glycolipid compound series. Several hypotheses are offered to explain the origins, implications and ethnobotanical significance of this unknown Commiphora sp., to the best of our knowledge the first identified from an archaeological site in this region, including identification with a resin producing tree mentioned in Biblical sources and possible agricultural relationship with the historic Judean Balsam.

Exploring the Mechanism of Myrrh in the Treatment of Breast Cancer Based on Network Pharmacology and Cell Experiments.

This study aimed to investigate the mechanism of action of myrrh in breast cancer (BC) treatment and identify its effective constituents. Data on the compounds and targets of myrrh were collected from the TCMSP, PubChem, and Swiss Target Prediction databases. BC-related targets were obtained from the Genecard database. A protein-protein interaction (PPI) analysis, gene ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted on the intersecting targets of the disease and drug. The key targets of myrrh in BC treatment were identified based on the PPI network. The active constituents of myrrh were determined through reverse-screening using the top 20 KEGG pathways. Macromolecular docking studies, molecular dynamic (MD) simulations, and cell assays were utilized to validate the active constituents and critical targets. Network pharmacology indicated that VEGFA, TP53, ESR1, EGFR, and AKT1 are key targets of myrrh. Pelargonidin chloride, Quercetin, and Naringenin were identified as the active constituents of myrrh. Macromolecular docking showed that Quercetin and Naringenin have strong docking capabilities with ESR1. The results of MD simulation experiments align with those of molecular docking experiments. Cell and western blot assays demonstrated that Quercetin and Naringenin could inhibit MCF-7 cells and significantly reduce the expression of ESR1 protein. The findings reveal the active constituents, key targets, and molecular mechanisms of myrrh in BC treatment, providing scientific evidence that supports the role of myrrh in BC therapy. Furthermore, the results suggest that network pharmacology predictions require experimental validation for reliability.

Optimization of antimicrobial nanocomposite films based on carboxymethyl cellulose incorporating chitosan nanofibers and Guggul gum polysaccharide.

The present study utilized response surface methodology (RSM) to investigate the impact of varying concentrations of carboxymethyl cellulose (CMC: 0.75-1.75 wt%), Commiphora mukul polysaccharide (CMP: 0-1 wt%), and Chitosan Nanofiber (CHNF: 0-1 wt%) on the physical and antimicrobial characteristics of nanocomposite films based on CMC. The optimization process aimed to enhance ultimate tensile strength (UTS), strain at break (SAB), and antibacterial activity, while minimizing water vapor permeability (WVP), solubility, swelling, moisture content, opacity, and total color difference (ΔE). The results revealed that both CMP and CHNF had a positive influence on reducing moisture content, WVP, and increasing UTS. However, higher concentrations of CMP and CHNF had a divergent effect on SAB, ΔE, and swelling. The incorporation of CMP led to increased opacity and solubility, while the inclusion of CHNF resulted in decreased opacity and solubility. Notably, only CHNF addition significantly improved the antibacterial properties of the films. By applying the optimization procedure utilizing RSM, the formulation containing CMC (1.5 wt%), CMP (0.25 wt%), and CHNF (0.75 wt%) demonstrated superior physical, mechanical, and antibacterial properties in the biodegradable film matrix. These findings highlight the potential of utilizing these components to enhance the performance of CMC-based nanocomposite films.

UPLC-qTOF-MS phytochemical profile of Commiphora gileadensis leaf extract via integrated ultrasonic-microwave-assisted technique and synthesis of silver nanoparticles for enhanced antibacterial properties.

The utilization of metallic nanoparticles in bio-nanofabrication holds significant potential in the field of applied research. The current study applied and compared integrated ultrasonic-microwave-assisted extraction (US/MICE), ultrasonic extraction (USE), microwave-assisted extraction (MICE), and maceration (MAE) to extract total phenolic content (TPC). In addition, the study examined the antioxidant activity of Commiphora gileadensis (Cg) leaf. The results demonstrated that the TPC of US/MICE exhibited the maximum value at 59.34 ± 0.007 mg GAE/g DM. Furthermore, at a concentration of 10 µg/mL, TPC displayed a significant scavenging effect on DPPH (56.69 %), with an EC50 (6.48 µg/mL). Comprehensive metabolite profiling of the extract using UPLC-qTOF-MS/MS was performed to identify active agents. A total of 64 chromatographic peaks were found, out of which 60 were annotated. The most prevalent classes of metabolites found were polyphenols (including flavonoids and lignans), organic compounds and their derivatives, amides and amines, terpenes, and fatty acid derivatives. Transmission electron microscopy (TEM) revealed the aggregate size of the synthesized nanoparticles and the spherical shape of C. gileadensis-mediated silver nanoparticles (Cg-AgNPs). The nanoparticles had a particle size ranging from 7.7 to 42.9 nm. The Cg-AgNPs exhibited more inhibition zones against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Cg-extract, AgNPs, and Cg-AgNPs were also tested. This study demonstrated the feasibility of using combined ultrasonic-microwave-assisted extraction to separate and extract chemicals from C. gileadensis on a large scale. These compounds have potential use in the pharmaceutical industry. Combining antibacterial and biocompatible properties in materials is vital for designing new materials for biomedical applications. Additionally, the results showed that the biocompatibility of the Ag-NPs using C. gileadensis extracts demonstrated outstanding antibacterial properties.

Guggulsterone protects against cigarette smoke-induced COPD linked lung inflammation.

Recently, we have shown that guggulsterone is the principal constituent responsible for protective effects of Commiphora wightii against elastase-induced chronic obstructive pulmonary disease (COPD)-linked inflammation/emphysema. Given that cigarette smoke (CS) exposure is a primary risk factor for COPD and beneficial effects of guggulsterone have not been investigated in CS-induced COPD-linked lung inflammation. The present work was designed to validate the potential of guggulsterone in amelioration of COPD-linked lung inflammation by using a CS-based mouse model of the condition. Male BALB/c mice were exposed to 9 cigarettes/day with 1 h interval for 4 days daily. Guggulsterone was administered daily at a dose of 10 mg/kg orally for 4 consecutive days, 1 h before initiation of CS exposure. Mice were subjected to measurement of lung function followed by procurement of bronchoalveolar lavage fluid (BALF)/lung tissue. BALF was analyzed for inflammatory cells and pro-inflammatory cytokines. Lung tissue was subjected to RT-PCR for gene expression analysis. Data showed that CS exposure resulted in a significant increase in total BALF cells, predominantly neutrophils, and macrophages. Interestingly, guggulsterone administration significantly blunted CS-induced inflammation as reflected by reduced neutrophil and macrophage count. Further, the compound inhibited CS-induced gene expression of pro-inflammatory mediators TNF-α/ IL-1ß/ G-CSF/and KC in lungs along with the production of pro-inflammatory mediators TNF-α/ IL-1ß/ IL-6/ G-CSF/ KC/and MCP-1 in BALF. Further, guggulsterone improved the lung function parameters upon CS exposure. Analysis of mRNA expression of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 suggests that guggulsterone may restore the fine balance between matrix-degrading proteases and its inhibitor in lung tissue upon CS exposure, which may contribute in the development of emphysema at later stages. Overall, our data show that guggulsterone protects against CS-induced COPD-linked lung inflammation by modulating relevant molecular players. Based on the potential effects of guggulsterone in the amelioration of CS-induced lung inflammation, we speculate that guggulsterone might alter chronic CS-induced emphysema.

Gas Chromatography-Mass Spectrometry Chemical Profiling of Commiphora myrrha Resin Extracts and Evaluation of Larvicidal, Antioxidant, and Cytotoxic Activities.

Plant extracts and essential oils can be alternative environmentally friendly agents to combat pathogenic microbes and malaria vectors. Myrrh is an aromatic oligum resin that is extracted from the stem of Commiphora spp. It is used in medicine as an insecticide, cytotoxic, and aromatic. The current study assessed the effect of Commiphora myrrha resin extracts on the biological potency of the third larval stage of Aedes aegypti, as well as its antioxidant and cytotoxic properties against two types of tumor cells (HepG-2 and Hela cell lines). It also used GC-MS to determine the chemical composition of the C. myrrha resin extracts. Fifty components from the extracted plant were tentatively identified using the GC-MS method, with curzerene (33.57%) typically listed as the primary ingredient, but other compounds also make up a significant portion of the mixture, including 1-Methoxy-3,4,5,7-tetramethylnaphthalene (15.50%), ß-Elemene (5.80%), 2-Methoxyfuranodiene (5.42%), 2-Isopropyl-4,7-Dimethyl-1-Naphthol (4.71%), and germacrene B (4.35%). The resin extracts obtained from C. myrrha exhibited significant efficacy in DPPH antioxidant activity, as evidenced by an IC50 value of 26.86 mg/L and a radical scavenging activity percentage of 75.06%. The 50% methanol extract derived from C. myrrha resins exhibited heightened potential for anticancer activity. It demonstrated substantial cytotoxicity against HepG-2 and Hela cells, with IC50 values of 39.73 and 29.41 µg mL-1, respectively. Notably, the extract showed non-cytotoxic activity against WI-38 normal cells, with an IC50 value exceeding 100 µg mL-1. Moreover, the selectivity index for HepG-2 cancer cells (2.52) was lower compared to Hela cancer cells (3.40). Additionally, MeOH resin extracts were more efficient against the different growth stages of the mosquito A. aegypti, with lower LC50, LC90, and LC95 values of 251.83, 923.76, and 1293.35 mg/L, respectively. In comparison to untreated groups (1454 eggs/10 females), the average daily number of eggs deposited (424 eggs/L) decreases at higher doses (1000 mg/L). Finally, we advise continued study into the possible use of C. myrrha resins against additional pests that have medical and veterinary value, and novel chemicals from this extract should be isolated and purified for use in medicines.

Light microscopical and parasitological analyses revealed the beneficial effects of silver nanoparticles and various myrrh extracts against Trichinella spiralis infection in mice.

Trichinella spiralis infection is a food-borne zoonotic disease caused by nematodes that dwell in the tissues, presenting a significant public health concern. This study aimed to evaluate the effectiveness of different treatments including silver nanoparticles (AgNPs), myrrh biosynthesized AgNPs "AgNPs synthesized using plant-based green technologies", myrrh extract, and myrrh essential oil, as alternative treatments against T. spiralis infection. Parasitological, histopathological, and cytotoxicity assessments were conducted to investigate the effects of various concentrations of these treatments in reducing the populations of adult worms and larvae during both the intestinal and muscular phases of T. spiralis-infected mice. The results showed that the highest antihelminthic efficacy against the intestinal phase of T. spiralis was achieved by myrrh extract (86.66%), followed closely by AgNPs (84.96%) and myrrh AgNPs (82.51%) at higher concentrations (800 mg/kg for myrrh extract, 40 µg/mL for AgNPs, and 40 µg/mL for myrrh AgNPs). While the group treated with myrrh essential oil showed the lowest percentage of adult reduction (78.14%). However, all treatments demonstrated comparable effects in reducing the larvae population in the muscle phase. Histopathological examination of the tissues revealed compelling evidence of the effectiveness of AgNPs, particularly when prepared with myrrh. Additionally, a comprehensive assessment of the cytotoxicity of AgNPs indicated low toxicity levels. This study supports that AgNPs synthesized using plant-based green technologies hold therapeutic potential for the treatment of T. spiralis infection. These findings present a promising avenue for the development of novel antiparasitic drugs that are both effective and safe. RESEARCH HIGHLIGHTS: Myrrh extract has the highest antihelminthic efficacy against the intestinal phase of T. spiralis. Histopathological examination of the tissues revealed compelling evidence of the effectiveness of AgNPs, particularly when prepared with myrrh. During intestinal phase of T. spiralis, varying levels of nanoparticle precipitation were detected in the liver, brain, lung, and intestine. During the muscular phase, the highest amount of AgNPs precipitation was detected in the liver, followed by the brain, and lung.

Ultrasonic-assisted extraction to enhance the recovery of bioactive phenolic compounds from Commiphora gileadensis leaves.

The "ultrasonic-assisted extraction (UAE)" method was utilized in this work to assess how different process parameters affected the yield and recovery of phenolic compounds from the leaf of Commiphora gileadensis, which is one of the medicinal plants with a variety of biological functions. Its leaf is used for a various of therapeutic applications, such as the treatment of bacterial infections, inflammation, and wound healing. The "One-Factor-At-a-Time (OFAT)" approach was employed to examine the impacts of various UAE process parameters on the process of extraction, which include time of extraction, sample/solvent ratio, ultrasonic frequency, and solvent (ethanol) concentration. The extracts were then investigated for the presence of several phytochemicals using analytical techniques such as "Gas Chromatography-Mass Spectroscopy (GC-MS)" and "Fourier Transform Infrared Spectroscopy (FTIR)" studies. The findings showed that the maximum extraction yield, the total phenolic content (TPC), and the total flavonoids content (TFC) of the ethanolic extract of the leaves of C. gileadensis using the UAE method were at 31.80 ± 0.41 %, 96.55 ± 2.81 mg GAE/g d.w. and 31.66 ± 2.01 mg QE/g d.w. accordingly under a procedure duration of 15 min, ultrasonic frequency of 20 kHz, solvent/sample ratio of 1:20 g/mL, and solvent concentration of 40 % v/v. The leaves extract of C. gileadensis included 25 phenolic compounds that were previously unreported, and GC-MS analysis confirmed their presence. Hence, it follows that the UAE technique can successfully extract the phytochemicals from C. gileadensis for a variety of therapeutic uses.

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.

In-vivo anti-diabetic and anti-hyperlipidemic effects of natural metabolites from resin of Commiphora mukul and their in-silico to in-vitro target fishing.

Diabetes mellitus is a rapidly spreading global metabolic disorder that has serious social, health, and economic consequences. Herein, we have evaluated in vivo antidiabetic and antihyperlipidemic effects of myrrhanone-B and myrrhanol-B (isolated from Commiphora mukul Hook). We observed that treatment with myrrhanone-B and myrrhanol-B at a dose of 5 and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and the concentration of blood glucose level (BGL) in alloxan (120 mg/kg) induced diabetic mice, which indicates that the compounds possess strong anti-diabetic activities. In the biochemical analysis, these compounds improved an abnormal level of total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL-C) to a normal level and increased the high-density lipoprotein cholesterol level (HDLC). Later, drug target of compounds was predicted through in-silico docking which shows that these compounds nicely fit in the active site of α-glucosidase enzyme and mediates excellent interactions with the catalytic residues, Asp214 and Asp349. The in-silico results were confirmed by in-vitro testing of myrrhanone-B and myrrhanol-B against α-glucosidase where both the compounds exhibited excellent inhibitory potency with IC50 values of 19.50 ± 0.71, and 16.11 ± 0.69 µM, respectively. Furthermore, mechanistic study was conducted to observe their binding mechanism, which reflect that myrrhanol-B has mixed type of inhibition (ki = 12.33 ± 0.030 µM), while myrrhanone-B demonstrates competitive type of inhibition (ki =14.53 ± 0.040 µM).

Protective effect of oleo-gum resin of Commiphora wightii against elastase-induced chronic obstructive pulmonary disease-linked lung inflammation and emphysema: Isolation and identification of key bioactive phytoconstituent.

ETHNOPHARMACOLOGICAL RELEVANCE: Oleo-gum resin of Commiphora wightii (Arnott) Bhandari of family Burseraceae, commonly known as 'guggul', is a well known Ayurvedic drug used traditionally to treat various disorders including respiratory ailments. However, role of C. wightii in chronic obstructive pulmonary disease (COPD) is not known. AIM: The present work was designed to investigate the protective potential of standardized C. wightii extract/and its fractions against elastase-induced COPD-linked lung inflammation and to identify key bioactive constituent(s). MATERIAL AND METHODS: C. wightii oleo-gum resin extract was prepared using Soxhlet extraction technique and the resultant extract was standardized on basis of guggulsterone content using HPLC. The extract was partitioned by different solvents in increasing order of polarity. Standardized extract/its partitioned fractions were orally administered to male BALB/c mice 1 h prior to intra-tracheal instillation of elastase (1U/mouse). Anti-inflammatory effect was evaluated by analyzing inflammatory cells and myeloperoxidase activity in lungs. The various fraction(s) were subjected to column chromatography to isolate bioactive compound. Isolated compound was identified using 1H and 13C-NMR and analyzed for assessment of several inflammatory mediators using techniques like ELISA, PCR, and gelatin zymography. RESULTS: C. wightii extract attenuated elastase-induced lung inflammation in dose-dependent manner and Ethyl acetate fraction (EAF) provided maximum protection. EAF was subjected to column chromatography followed by assessment of bioactivity of each sub-fraction, ultimately leading towards isolation of two compounds i.e. C1 and C2. C1 seems to be the key active principle of C. wightii, as it displayed significant anti-inflammatory activity against elastase induced lung inflammation while C2 largely remains ineffective. C1 was identified as mixture of E- and Z-guggulsterone (GS). Reduction in the elastase induced lung inflammation by GS was associated with downregulation of expression of several COPD linked pro-inflammatory factors such as IL-6/TNF-α/IL-1ß/KC/MIP-2/MCP-1/G-CSF as well as normalization of redox imbalance as indicated by levels of ROS/MDA/protein carbonyl/nitrite/GSH etc. Further, 21 days prolonged administration of GS (10 mg/kg b.wt; once daily) protected against elastase-induced emphysema by mitigating expression/activity of MMP-2/-9 and increasing TIMP-1 expression. CONCLUSION: Overall, guggulsterone seems to be the key bioactive constituent responsible for exerting beneficial effects of C. wightii against COPD.

Sesquiterpenoids from the Resina Commiphora Promoting the Apoptotic Activity of PC-3 Prostate Cancer Cells.

Four new germacrane-type sesquiterpenes commiphoranes M1-M4 (1-4) together with eighteen sesquiterpenes were isolated from the Resina Commiphora. The structures and relative configurations of new substances were determined by using spectroscopic methods. Biological activity investigation revealed that nine compounds including 7, 9, 14, 16, (+)-17, (-)-17, 18, 19, and 20 could induce the apoptosis of prostate cancer originated PC-3 cells, through classic apoptosis signaling pathway, even using flow cytometry showed that the compound (+)-17 caused apoptosis of PC-3 cells more than 40 %, suggesting their potential therapeutic application in the development of novel drugs against prostate cancer.

Exploring the Chemical Constituents, Antioxidant, Xanthine Oxidase and COX Inhibitory Activity of Commiphora gileadensis Commonly Grown Wild in Saudi Arabia.

The use of the synthetic drugs has increased in the last few decades; however, these drugs exhibit various side effects. Scientists are therefore seeking alternatives from natural sources. Commiphora gileadensis has long been used to treat various disorders. It is commonly known as bisham or balm of Makkah. This plant contains various phytochemicals, including polyphenols and flavonoids, with biological potential. We found that steam-distilled essential oil of C. gileadensis exhibited higher antioxidant activity (IC50, 22.2 µg/mL) than ascorbic acid (IC50, 1.25 µg/mL). The major constituents (>2%) in the essential oil were ß-myrcene, nonane, verticiol, ß-phellandrene, ß-cadinene, terpinen-4-ol, ß-eudesmol, α-pinene, cis-ß-copaene and verticillol, which might be responsible for the antioxidant and antimicrobial activity against Gram-positive bacteria. The extract of C. gileadensis exhibited inhibitory activity against cyclooxygenase (IC50, 450.1 µg/mL), xanthine oxidase (251.2 µg/mL) and protein denaturation (110.5 µg/mL) compared to standard treatments, making it a viable treatment from a natural plant source. LC-MS analysis revealed the presence of phenolic compounds such as caffeic acid phenyl ester, hesperetin, hesperidin, chrysin and transient amounts of catechin, gallic acid, rutin and caffeic acid. The chemical constituents of this plant can be explored further to investigate its wide variety of therapeutic potential.

Terpenoids from Myrrh and Their Cytotoxic Activity against HeLa Cells.

The oleo-gum resin of Commiphora myrrha (Nees) Engl. has a long history of medicinal use, although many of its constituents are still unknown. In the present investigation, 34 secondary metabolites were isolated from myrrh resin using different chromatographic techniques (silica flash chromatography, CPC, and preparative HPLC) and their structures were elucidated with NMR spectroscopy, HRESIMS, CD spectroscopy, and ECD calculations. Among the isolated substances are seven sesquiterpenes (1-7), one disesquiterpene (8), and two triterpenes (23, 24), which were hitherto unknown, and numerous substances are described here for the first time for C. myrrha or the genus Commiphora. Furthermore, the effects of selected terpenes on cervix cancer cells (HeLa) were studied in an MTT-based in vitro assay. Three triterpenes were observed to be the most toxic with moderate IC50 values of 60.3 (29), 74.5 (33), and 78.9 µM (26). Due to the different activity of the structurally similar triterpenoids, the impact of different structural elements on the cytotoxic effect could be discussed and linked to the presence of a 1,2,3-trihydroxy substructure in the A ring. The influence on TNF-α dependent expression of the intercellular adhesion molecule 1 (ICAM-1) in human microvascular endothelial cells (HMEC-1) was also tested for 4-6, 9-11, 17, 18, 20, and 27 in vitro, but revealed less than 20% ICAM-1 reduction and, therefore, no significant anti-inflammatory activity.

Commiphora wildii Merxm. Essential Oil: Natural Heptane Source and Co-Product Valorization.

As an alternative to fossil volatile hydrocarbon solvents used nowadays in perfumery, investigation on essential oil of Commiphora wildii Merxm. oleo gum resin as a source of heptane is reported here. Heptane, representing up to 30 wt-% of this oleo gum resin, was successfully isolated from the C. wildii essential oil, using an innovative double distillation process. Isolated heptane was then used as a solvent in order to extract some noble plants of perfumery. It was found that extracts obtained with this solvent were more promising in terms of sensory analysis than those obtained from fossil-based heptane. In addition, in order to valorize the essential oil depleted from heptane, chemical composition of this oil was found to obtain, and potential biological activity properties were studied. A total of 172 different compounds were identified by GC-MS in the remaining oil. In vitro tests-including hyaluronidase, tyrosinase, antioxidant, elastase and lipoxygenase, as well as inhibitory tests against two yeasts and 21 bacterial strains commonly found on the skin-were carried out. Overall, bioassays results suggest this heptane-depleted essential oil is a promising active ingredient for cosmetic applications.

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.

The anti-inflammatory effect of myrrh ethanolic extract in comparison with prednisolone on an autoimmune disease rat model induced by silicate.

Autoimmune disease is a complex chronic disease that triggers immune activation against autoantigens resulting in tissue damage. Epidemiological data showed that autoimmune diseases are increasing worldwide over the last decades owing to increased environmental pollution. This study investigates the therapeutic effect of myrrh as a natural medicine compared to prednisolone in the treatment of immune-mediated glomerulonephritis induced by silicate. The autoimmune disease model in rats was induced by injecting 5 mg crystalline sodium silicate suspension subcutaneously once weekly for 20 weeks, and then the rats were treated either with myrrh extract or prednisolone or with both for 6 weeks. Liver and kidney function tests, histopathology, and immunohistochemistry of TNF-α expression in kidney tissue were performed. The creatinine significantly elevated in silica-treated group and decreased in other treated groups. Histopathology of the kidney revealed improvement of glomerular and tubular basement thickness in all treated groups, but the inflammatory cell count slightly decreased in the group treated with myrrh than the other treated groups which showed a marked decrease. TNF-α expression was significantly decreased in all treated groups. Interestingly, the myrrh did not produce hepatic lesions and improve the side effect of prednisolone in the liver when taken in combination. Therefore, myrrh extract possessed anti-inflammatory properties and counteracted the side effect of prednisolone on the liver. Myrrh extract can serve as a conjunctive therapy with prednisolone to treat autoimmune diseases.

Chemical compositions of Commiphora opobalsamum stem bark to alleviate liver complications in streptozotocin-induced diabetes in rats: Role of oxidative stress and DNA damage.

CONTEXT: Hyperglycaemia plays an important role in the development of non-alcoholic fatty liver disease, which is a common complication in diabetics. OBJECTIVE: The present study aimed to investigate the chemical composition and the efficacy of Commiphora opobalsamum stem bark butanol fraction in ameliorating liver injury associated with diabetes induced by streptozotocin (STZ) in rats. MATERIALS AND METHODS: The butanol fraction was applied to high-performance liquid chromatography-mass spectrometry (HPLC/MSn) to identify the most bioactive metabolites. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight), while treatment with the plant extract was performed (100 mg/kg body weight) for three weeks after diabetic induction for one month. RESULTS: Thirty eight metabolites were tentatively identified from the butanol fraction of C. opobalsamum stem bark. Insulin, glutathione, superoxide dismutase, and high density lipoprotein levels in diabetic rats were significantly low (p < 0.05), while glucose, α-amylase, malondialdehyde, aspartate and alanine aminotransferases, cholesterol, triglycerides, low density lipoprotein, tumour necrosis factor-α, interleukin-6, and DNA fragmentation levels were significantly high. Treatment with the plant extract showed improvements in the seleced parameters by variable degrees. Conclusion: The plant extract is considered as a promising natural therapeutic agent against liver injury, hyperglycemia, oxidative stress, inflammation, hyperlipidaemia, and DNA damage.