Four new resin glycosides from Ipomoea muricata seeds: muricatins XIV-XVII.

Ipomoea muricata (L.) Jacq. seeds (Convolvulaceae) are used as a traditional laxative and carminative medicine. Muricatins XIV (1), XV (2), XVI (3), and XVII (4), were isolated from I. muricata seeds as four new resin glycosides, along with seven known compounds, three of which were isolated for the first time as natural products; their structures were determined using MS and NMR spectroscopy. Compounds 1-4 are macrolactones (jalapins); the sugar moieties of 1, 2, and 4 are partially acylated with 2S-methylbutyric acid, while that of 3 is esterified with 2S-methylbutyric and 2S-methyl-3S-hydroxybutyric acids. In addition, the antiviral activities of the seven compounds obtained in this study, together with five known compounds obtained in our previous study into resin glycosides from I. muricata seeds, were evaluated against herpes simplex virus type 1 (HSV-1); their cytotoxicities against HL-60 human promyelocytic leukemia cells were also investigated. All examined jalapins exhibited similar or slightly weaker anti-HSV-1 activities than acyclovir, the positive control; however, the glycosidic acid of 4 was inactive, while its methyl ester was weakly active. On the other hand, cytotoxicity testing against HL-60 cells showed similar results to those observed during anti-HSV-1 activity testing, with the exception that one jalapin was less active.

Recovery and separation of glycyrrhizic acid from Natural Deep Eutectic Solvent (NADES) extract by macroporous resin: adsorption kinetics and isotherm studies.

Natural Deep Eutectic Solvents (NADESs) have emerged as a green and sustainable alternative to conventional organic solvents to extract bioactive compounds. However, the recovery of bioactive compounds from the NADES extracts is challenging, restricting their large-scale applications. The present work investigated the recovery of glycyrrhizic acid (GA) from choline-chloride/lactic acid NADES extract using macroporous resins. GA possesses a wide spectrum of biological activities, and it is extracted from the well-known herb Glycyrrhiza glabra. During resin screening, DIAIONTM SP700 showed high adsorption and desorption capacities. The adsorption kinetics study demonstrated that the adsorption of GA on SP700 followed Pseudo First-order kinetic model. Moreover, the adsorption behaviors were elucidated by the Freundlich isotherm using a correlation coefficient based on a static adsorption study at different temperatures and pH. Furthermore, the thermodynamic parameters, for instance, the change of Gibbs free energy (ΔG*), entropy (ΔS*), and enthalpy (ΔH*), showed that the adsorption process was spontaneous, favorable and exothermic. In addition, the sample after macroporous resin treatment, which is enriched with GA exhibited good anticancer potential analyzed by SRB assay. The regenerated NADES solvent was recycled twice, keeping more than 90% extraction efficiency, indicating good reusability of NADES in the GA extraction process by using macroporous resin.

Inhibition of multidrug-resistant MCF-7 breast cancer cells with combinations of clinical drugs and resin glycosides from Operculina hamiltonii.

The jalap roots, Operculina hamiltonii D.F. Austin & Staples (Convolvulaceae), are extensively commercialized as a depurative and laxative remedy in traditional medicine of the north and northeast regions of Brazil. The purification by recycling HPLC and structure elucidation of three new acyl sugars or resin glycosides are described here from a commercial product made of powdered roots. Three macrocyclic structures of a tetrasaccharide of (11S)-hydroxyhexadecanoic acid, operculinic acid C (1), the undescribed hamiltonins II and III (3 and 4), in addition to the known batatinoside III (5), presented a diastereoisomeric relationship as one residue of n-dodecanoic acid esterified the oligosaccharide core on a different position in each compound. Furthermore, hamiltonin IV (6) was characterized as an ester-type homodimer of acylated operculinic acid C with the same substitution pattern identified in hamiltonins II (3) and III (4) for each of the dimer subunits. All the isolated resin glycosides did not display any intrinsic cytotoxicity (IC50 > 25 µM). However, a combination of the individual isolated compounds 3-6 (1-50 µM) demonstrated an enhancement of cytotoxic effects with sublethal doses of vinblastine and podophyllotoxin (0.003 µM) in multidrug-resistant breast carcinoma epithelial cells (MCF-7/Vin).

Antitumor and Phytochemical Properties of Ferula assa-foetida L. Oleo-Gum-Resin against HT-29 Colorectal Cancer Cells In Vitro and in a Xenograft Mouse Model.

Colorectal cancer (CRC) is one of the most frequently occurring tumors. Ferula assa-foetida oleo-gum-resin (OGR) extract is a traditional cooking spice known for its broad spectrum of biological activities such as antifungal, antiparasitic, and anti-inflammatory activities. This study evaluated the antitumor effect of OGR extract against HT-29 colorectal cancer cells. The OGR chemical composition was analyzed using LC-ESI-MS/MS; MTT, clonogenic assays, and a xenograft model were used to measure cytotoxicity, while apoptotic proteins were detected using Western blotting. Phytochemical analysis revealed that the extract was a rich source of isoflavones, xanthones, and other derivatives. In a dose-dependent manner, the OGR extract significantly inhibited colony formation ability and HT-29 cell growth (IC50 was 3.60 ± 0.02 and 10.5 ± 0.1 mg/mL, respectively). On the other hand, the OGR extract significantly induced apoptosis and increased the expression of some pro-death proteins involved in cellular apoptosis including PUMA, BIM, BIK, and BAK. Moreover, in a subcutaneous HT-29 xenograft model, the tumor volume and burden decreased after treatment with the OGR extract (550 ± 32 mm3 and 16.3 ± 3.6, respectively) This study demonstrated that Ferula assa-foetida OGR ethanolic extract has potential antitumor effects against HT-29 CRC cell lines by reducing cell viability and the function of apoptosis. More studies are needed to reveal the underlying mechanisms related to cytotoxicity and apoptosis induction.

Phytochemical study of Boswellia dalzielii oleo-gum resin and evaluation of its biological properties.

Boswellia dalzielii is a resin-producing tree endemic to West and Central Africa, used by local populations for various medicinal purposes. In this study, B. dalzielii gum resin was analyzed by GC-MS and UHPLC-MS to identify and quantify volatile and non-volatile compounds. Its main volatile constituents were α-pinene (54.9%), followed by α-thujene (4.4%) and α-phellandren-8-ol (4.0%). Pentacyclic triterpenoids such as ß-boswellic acids and their derivatives were quantified by UHPLC-MS and their content was shown to reach around 22% of the gum resin. Since some of the volatile and non-volatile compounds identified in this work are known to possess biological effects, the bioactivities of B. dalzielii ethanolic extract, essential oil, as well as fractions of the oil and extract were evaluated. Some of these samples exhibited interesting anti-inflammatory properties, and their antioxidant, anti-ageing and skin-bleaching activities were also tested.

Five new resin glycosides, calyhedins XI-XV, from Calystegia hederacea.

Calystegia hederacea Wall. (Convolvulaceae) is a perennial herbaceous vine that grows widely in India and East Asia. All parts of this plant are used to treat various disorders such as menoxenia and gonorrhea. Four new resin glycosides, calyhedins XI (1)-XIV (4), were isolated from the rhizomes of C. hederacea. A new glycoside, calyhedin XV (5), was isolated from its leaves and stems. Alkaline hydrolysis of 1 and 2 furnished a new glycosidic acid, calyhedic acid G (1a), from 1 and a new acid, calyhedic acid H (2a), from 2 along with 2S-methylbutyric acid and 2R-methyl-3R-hydroxybutyric (2R,3R-nilic) acid. The structures of 1-5, 1a, and 2a were determined using MS and NMR spectral analyses. Compounds 1a and 2a had the same sugar moiety, ß-D-glucopyranosyl-(1 → 6)-O-ß-D-glucopyranosyl-(1 → 6)-O-ß-D-glucopyranosyl-(1 → 3)-[O-ß-D-glucopyranosyl-(1 → 3)-O-α-L-rhamnopyranosyl-(1 → 2)]-O-ß-D-glucopyranosyl-(1 → 2)-ß-D-fucopyranose, while their aglycones were 11S-dihydroxyhexadecanoic acid and 12S-dihydroxyhexadecanoic acid, respectively. These compounds are the first glycosidic acids, with fucose as the monosaccharide component obtained from the resin glycosides of C. hederacea. Compounds 1-5, comprising either 1a or 2a, were heptaglycosides with macrolactone structures, and their sugar moieties were partially acylated with 5 mol of organic acids comprising 2S-methylbutyric, (E)-2-methylbut-2-enoic, and 2R,3R-nilic acids. Compounds 1 and 5 had 22-membered rings, while 2-4 had 28-membered rings. In addition, 1 and 5 exhibited cytotoxic activity against HL-60 human promyelocytic leukemia cells, comparable to that of the positive control cisplatin.

Hederifolic acids A-D, hepta and hexasaccharides from the resin glycosides of Ipomoea hederifolia.

Scarlet morning glory, Ipomoea hederifolia L. (Convolvulaceae), is an ornamental vine native to the Americas with oxytocic, cytotoxic, antipsychotic, anti-inflammatory, antioxidant, and antimicrobial properties. A chemical study of the glycosidic acids from the resin glycosides contained in the aerial parts was carried out, through their isolation as peracetylated derivatives, by recycling preparative liquid chromatography. Structure elucidation was performed by HR-MS in accordance with NMR. Four peracetylated derivatives of glycosidic acids, named hederifolic acids A-D, were identified as heptaglycosides and hexaglycosides linked to 3S,12S-dihydroxyheptadecanoic acid or 12 S-hydroxyheptadecanoic acid. Consequently, hederifolic acids B and D were found to be dehydroxylated homologs at C-3 of the fatty acid aglycones of hederifolic acids A and C, respectively.

Comparative phytochemical analysis of Ferula assa-foetida with Ferula jaeschkeana and commercial oleo-gum resins using GC-MS and UHPLC-PDA-QTOF-IMS.

Ferula assa-foetida is an important species of the genus Ferula, best known for its oleo-gum resin, mainly used as a flavoring agent. Ferula jaeschkeana is another Himalayan medicinal plant of this genus, known for its contraceptive effect but not used in food applications. This study aimed to do a detailed phytochemical analysis of F. assa-foetida growing under controlled conditions in India using GC-MS/headspace and UHPLC-PDA-QTOF-IMS. Further, a comparative analysis of F. assa-foetida was performed with F. jaeschkeana (collected from its natural habitat) and commercial samples of F. assa-foetida oleo-gum resin (collected from the local market). UHPLC-QTOF-IMS profiling of F. assa-foetida led to the identification of foetisulfide C, assafoetidnol A, gumosin, flabellilobin (A/B), and foetisulfide A. In total, 141 metabolites were identified, including vitamins, nucleosides, sulfur compounds, flavonoids, sugars derivatives, and others, using METLIN database. Serine, arginine, asparagine, isoleucine, and phenylalanine were major amino acids quantified among the samples for the nutritional aspect. Characteristic sulfurous compounds (n-propyl-sec-butyl disulfide, trans-propenyl-sec-butyl disulfide, cis-propenyl-sec-butyl disulfide, and bis[1-(methylthio)propyl] disulfide) were identified in all samples except F. jaeschkeana. PCA and cluster analysis showed a significant difference in the volatile constituents of rhizomes of both species. Metabolomics studies also revealed the association of sesquiterpenoid and triterpenoid biosynthesis, phenylpropanoid, flavon, and flavanol biosynthesis. The current study demonstrates, "why only F. assa-foetida is used in culinary applications instead of F. jaeschkeana"?

Successful identification of the species of the semipetrified amber medicinal resin benzoin using molecular diagnostic technology.

Benzoin is an incomplete lithified resin secreted from the trunk of the Styrax Linn. that is known as "semipetrified amber" and has been widely used in medicine due to its blood circulation-promoting and pain-relieving properties. However, the lack of an effective species identification method due to the numerous sources of benzoin resin and the difficulty of DNA extraction has led to the uncertainty of species of benzoin in the trade process. Here, we report the successful extraction of DNA from benzoin resin containing bark-like residues and the evaluation of commercially available benzoin species using molecular diagnostic techniques. By performing a BLAST alignment of ITS2 primary sequences and homology prediction analysis of ITS2 secondary structures, we found that commercially available benzoin species were derived from Styrax tonkinensis (Pierre) Craib ex Hart. and Styrax japonicus Sieb. et Zucc. of the genus Styrax Linn. In addition, some of the benzoin samples were mixed with plant tissues from other genera, accounting for 29.6%. Therefore, this study provides a new method to solve the problem of species identification of semipetrified amber benzoin using information from bark residues.

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.

Bioassay-guided preparation of antioxidant, anti-inflammatory active fraction from crabapples (Malus prunifolia (Willd.) Borkh.).

The aim of current study was to optimize the extraction process and purification of main components (MC) to obtain high antioxidant, anti-inflammatory effective fractions from crabapple (Malus prunifolia (Willd.) Borkh.). The effects of three variables including ethanol concentration A1, solid-liquid ratio A2, extraction temperature A3 were investigated and optimized by response surface methodology (RSM) coupled with Box-Behnken design (BBD). The adsorption/desorption characteristics of MC on the five types of macroporous resins were investigated. According to batch adsorption test, HPD-300 resins were selected for kinetics. The adsorption mechanism showed that the process was appropriate by pseudo-second-order kinetics model, and purification parameters of MC were optimized through adsorption/desorption experiments with the column packed by HPD-300 resin. The effective fractions were obviously superior to other fractions according to DPPH, ABTS, COX-2 and 15-LOX radical scavenging. This work implies that the purified active fraction with high contents of antioxidants and anti-inflammatory compounds from crabapple might be potential source for natural products and food industries.

Synthesis and Structure Revision of Naturally Occurring Homoisoflavane (+)-Dracaeconolide B.

Dracaeconolide B (1), a naturally occurring homoisoflavane, was isolated from the red resin of Dracaena cochinchinensis. Efforts have been made to elucidate the exact structure of compound 1 since it was confirmed that dracaeconolide B did not contain a 7-hydroxy-5,8-dimethoxy moiety. The structure of dracaeconolide B was revised by synthesis of three homoisoflavanes containing a 5,6,7-trioxygenated moiety each and analysis by NMR spectroscopy. The revised structure of dracaeconolide B was proposed as 3-(4-hydroxybenzyl)-7-hydroxy-5,6-dimethoxychromane. Noyori's Ru-catalyzed asymmetric transfer hydrogenation was used to synthesize (+)-dracaeconolide B. The absolute configuration of the compound was revised to S based on the results obtained by the electronic circular dichroism calculation. We examined the antiangiogenic activity of (S)- and (R)-dracaeconolide B and of synthetic 5,6,7- and 5,7,8-trioxygenated homoisoflavanes. The results can potentially help in the synthesis of related natural products and support drug discovery to treat neovascular eye diseases.

Identification and characterization of organic and glycosidic acids in the crude resin glycoside fraction from the leaves and stems of Calystegia japonica.

The alkaline hydrolysis of the crude resin glycoside fraction from the leaves and stems of the plant Calystegia japonica Choisy (Convolvulaceae) yielded organic acid and glycosidic acid fractions. The organic acid fraction was esterified with p-bromophenacyl bromide to obtain p-bromophenacyl 2R-methyl-3R-hydroxybutyrate (1) and p-bromophenacyl (E)-2-methylbut-2-enoate (2). By treating the glycosidic acid fraction with trimethylsilyldiazomethane-hexane, seven new methyl esters of glycosidic acids, namely calyjaponic acid A methyl ester (3) calyjaponic acid B methyl ester (5), calyjaponic acid C methyl ester (6), calyjaponic acid D methyl ester (7), calyjaponic acid E methyl ester (8), calyjaponic acid F methyl ester (9), and calyjaponic acid G methyl ester (10), were isolated along with one known ester (4). Their structures were characterized based on spectroscopic and chemical analyses. Compounds 3-8 had the same sugar moiety, α-L-rhamnopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-(1 → 2)-[O-α-L-rhamnopyranosyl-(1 → 6)]-O-ß-D-glucopyranose, and the aglycones of 3-8 were methyl 3S,11S-dihydroxyhexadecanoate, methyl 3S,12S-dihydroxyhexadecanoate, methyl 11S-hydroxyhexadecanoate, methyl 11S-hydroxypentadecanoate, methyl 3S,11S-dihydroxypentadecanoate, and methyl 3S,12S-dihydroxypentadecanoate, respectively. Compounds 9 and 10 were derivatives of 3 and 4, respectively, in which the C-6 of the second glucosyl residue was methylated. Compounds 6-8 contained methyl esters of unusual odd-carbon fatty acids as aglycones. The cytotoxicity of the crude resin glycoside fraction and 3 against HL-60 human promyelocytic leukemia cells was evaluated further; both were either weakly active or inactive compared to the positive control, cisplatin.

Enhanced intradermal delivery of Dragon's blood in biocompatible nanosuspensions hydrogel patch for skin photoprotective effect.

Dragon's Blood is a member of the Chinese medicinal herb, having anti-oxygen and anti-inflammatory activity for the photoprotective effect. However, the poor water solubility of raw Dragon's Blood powder has limited its intradermal delivery process. In this study, we evaluated nanosuspensions to enhance intradermal delivery of Dragon's Blood exerting a photoprotective effect. The prepared nanosuspension was added to a composite hydrogel patch matrix for better skin application. In the present research, we used biocompatible materials hyaluronic acid and amino acid surfactants as nanosuspension stabilizers and agar/gelatin/sodium polyacrylate as hydrogel patch matrix. The prepared Dragon's Blood nanosuspension had a particle size of 447.0 ± 48.6 nm. The micro-structures morphology and viscoelasticity characteristics by SEM and rheological testing confirmed a sufficient crosslinked hydrogel network. The skin retention amount of Dragon's Blood nanosuspension was 1.48 times of raw Dragon's Blood powder water suspension, and the skin penetration amount of Dragon's Blood nanosuspension was only about 1/3 of Dragon's Blood DMSO solution. In the UVB-irradiated HaCaT cell phototoxicity model, Dragon's Blood nanosuspension also significantly increased cell viability by about 1 time of the model group and decreased the production of reactive oxygen species about 1/2 times of model group. In vivo safety and efficiency evaluation experiment illustrated that DB-NS hydrogel patch processes have favorable safety and photoprotective effect with no skin irritancy and phototoxicity. Furthermore, DB-NS and DB-NS hydrogel patches could protect skin from UVA and UVB irritating skin reactions. Overall, our study of the combined use of biocompatible and biodegradable materials as excipients of nanosuspension and hydrogel patch could be used as an effective additive of Intradermal delivery and skin photoprotection.

Frankincense-Myrrh treatment alleviates neuropathic pain via the inhibition of neuroglia activation mediated by the TLR4/MyD88 pathway and TRPV1 signaling.

BACKGROUND: Neuroglia are important modulators of neuronal functionality, and thus play an integral role in the pathogenesis and treatment of neuropathic pain (NP). According to traditional Chinese medicine, Frankincense-Myrrh is capable of "activating blood and dissipating blood stasis", and as such these two biological compounds are commonly used to treat NP, however, the mechanisms underlying the efficacy of such treatment are unclear. PURPOSE: This study aimed to further elucidate the protective effects associated with the Frankincense-Myrrh treatment of NP. METHODS: A chronic sciatic nerve compression injury (CCI) model of NP was established, after which animals were gavaged with Frankincense, Myrrh, Frankincense-Myrrh, or the positive control drug pregabalin for 14 days. Network pharmacology approaches were used to identify putative pathways and targets associated with the Frankincense-Myrrh-mediated treatment of NP, after which these targets were subjected to in-depth analyses. The impact of TLR4 blockade on NP pathogenesis was assessed by intrathecally administering a TLR4 antagonist (LRU) or the MyD88 homodimerization inhibitory peptide (MIP). RESULTS: Significant alleviation of thermal and mechanical hypersensitivity in response to Frankincense and Myrrh treatment was observed in NP model mice, while network pharmacology analyses suggested that the pathogenesis of NP may be related to TLR4/MyD88-mediated neuroinflammation. Consistently, Frankincense-Myrrh treatment was found to reduce TLR4, MyD88, and p-p65 expression in spinal dorsal horn neuroglia from treated animals, in addition to inhibiting neuronal TRPV1 and inflammatory factor expression. Intrathecal LRU and MIP delivery were sufficient to alleviate thermal and mechanical hyperalgesia in these CCI model mice, with concomitant reductions in neuronal TRPV1 expression and neuroglial activation in the spinal dorsal horn. CONCLUSION: These data suggest that Frankincense-Myrrh treatment was sufficient to alleviate NP in part via inhibiting TLR4/MyD88 pathway and TRPV1 signaling activity. Blocking TLR4 and MyD88 activation may thus hold value as a means of treating NP.

[Combination characteristics of frankincense and myrrh and progress and prospect of their combination efficacy and mechanism].

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.

An Effective Chromatography Process for Simultaneous Purification and Separation of Total Lignans and Flavonoids from Valeriana amurensis.

An effective chromatography process was developed and validated for simultaneous purification and separation of total lignans and flavonoids from Valeriana amurensis. The total lignans and flavonoids in Valeriana amurensis extract were prepurified with macroporous resin column chromatography, and the conditions were optimized as follows: 40 mg/mL Valeriana amurensis extract (2.0 g) solution was loaded onto an AB-8 resin column with a diameter-to-height ratio of 1:7, followed by adsorption for 6 h; then, the column was eluted successively with 5 BV water and 10% and 50% ethanol at a flow rate 2 BV/h. The obtained 50% ethanol fraction was further repurified and separated by polyamide resin column chromatography to obtain the total lignans and flavonoids, respectively. The chromatography conditions were optimized as follows: a 50% ethanol fraction (1.0 g) was mixed with 1.0 g polyamide resin and loaded onto a polyamide resin (60-100 mesh) column with a diameter-to-height ratio of 1:3; then, the column was eluted successively with 6 BV water and 40% and 80% ethanol at a flow rate of 4 BV/h. The total lignans and flavonoids were obtained from water and 80% ethanol fraction, respectively. The content and recovery of standard compounds in total lignans and flavonoids were analyzed with HPLC-PDA, and the feasibility of the process was confirmed.

Resin Glycosides from Operculina hamiltonii and Their Synergism with Vinblastine in Cancer Cells.

Operculina hamiltonii is a vine native to the north and northeast region of Brazil, where its roots are traded as a depurative and laxative remedy with the name of Brazilian jalap in traditional medicine. Procedures for the isolation, purification by recycling HPLC, and structure elucidation of three undescribed resin glycosides are presented herein. Hamiltonin I (1) represents a macrocyclic structure of a tetrasaccharide of (11S)-hydroxyhexadecanoic acid. Additionally, two acyclic pentasaccharides, named hamiltoniosides I (2) and II (3), were also isolated, which are related structurally to the known compounds 4 and 5, macrocyclic lactone-type batatinosides. The tetrasaccharide core of 1 was diacylated by n-decanoic acid and the unusual n-hexadecanoic acid moiety, while the pentasaccharides 2-5 were esterified by one unit of n-decanoic or n-dodecanoic acid. All the isolated compounds were found to be inactive as cytotoxic agents. However, when they were evaluated (1-25 µM) in combination with a sublethal concentration of the anticancer agent vinblastine (0.003 µM), a significant enhancement of the resultant cytotoxicity was produced, especially for multidrug-resistant breast carcinoma epithelial cells. Such combined synergistic potency may be beneficial for chemotherapy, making resin glycosides potential candidates for drug repurposing of conventional chemotherapeutic drugs to reduce their side effects.

Phytochemical Composition of Commiphora Oleogum Resins and Their Cytotoxicity against Skin Cancer Cells.

Oleogum resins of the genus Commiphora have been used in traditional medicines for centuries. More than 200 Commiphora species exhibit highly variable phytochemical compositions. A novel highly selective, sensitive, accurate HPLC-MS/MS method was developed and validated to quantify five characteristic phytosteroids and furanosesquiterpenoids, namely (E)-guggulsterone, (Z)-guggulsterone, curzerenone, furanoeudesma-1,3-diene, and myrrhone. The resulting contents and additionally GC analysis were used to classify and differentiate Commiphora oleogum resins of the species C. myrrha, C. erythraea, C. mukul, C. holtziana, C. confusa, and C. kua, as well as unspecified resins. Interestingly, a Commiphora sample from Ogaden, Ethiopia, comprised 446 ng/mg guggulsterones presumed to be unique to C. mukul from the Indian subcontinent. However, Commiphora from Ogaden differed considerably from C. mukul in respect to guggulsterones isomer's ratio. Moreover, the cytotoxicity of Commiphora extracts, essential oils, botanical drugs containing Commiphora, and pure compounds against the epidermoid carcinoma A431, malignant melanoma RPMI-7951 and SK-MEL-28 cells was investigated in vitro. Thereby, especially C. mukul extract and C. myrrha essential oil exhibited high cytotoxicity against skin cancer cells with IC50 of 2.9-10.9 µg/mL, but were less toxic to normal keratinocytes. In summary, Commiphora oleogum resins and its phytochemicals warrant further investigation aiming at chemotaxonomical classification as well as application in skin cancer treatment.

Tracing analgesic constituents from crude and vinegar-processed resin of Boswellia carterii by integrating ultra-performance liquid chromatography tandem mass spectrometry-based determination, analgesic evaluation in mice, and gray relationship analysis.

The analgesic effect of the resin of Boswellia carterii (BC) is well known; however, the constituents that contribute to the analgesic effect remain elusive. The current study integrates ultrasonic-assisted extraction, quantitative determination, analgesic evaluation in rats, and gray relationship analysis for tracing analgesic constituents from the resin of BC. First, a robust and precise ultra-performance liquid chromatography tandem mass spectrometry approach with multiple reaction monitoring mode was developed for the simultaneous quantification of seven major constituents in crude and vinegar-processed resin of BC. Glycyrrhetinic acid was chosen as the internal standard. The approach showed good linearity. The intra- and inter-day precisions of each constituent were within 3.0%. The recoveries of each constituent were in the range of 96.4-102.7%. The approach was then applied to determine the seven constituents in 10 batches of crude and vinegar-processed resin of BC. Second, the analgesic effects of crude and vinegar-processed resin of BC were assessed in mice. Third, chemometrics methods, gray relationship analysis, and partial least squares regression were employed for determining the relationship between the contents of seven constituents and their analgesic effects. 11-Keto-ß-boswellic acid, 3-acetyl-ß-boswellic acid, 3-acetyl-α-boswellic acid, 3-acetyl-11-keto-ß-boswellic acid, and ß-sitosterol were identified as the key analgesic constituents of BC.