Identification and structural modification of ent-rosane diterpenoids from Euphorbia milii inhibiting RANKL-induced osteoclastogenesis.

Phytochemical study on Euphorbia milii, a common ornamental plant, resulted in the identification of thirteen new ent-rosane diterpenoids (1-13), three new ent-atisane diterpenoids (14-16), and a known ent-rosane (17). Their structures were delineated using spectroscopic data, quantum chemical calculations, and X-ray diffraction experiments. Euphomilone F (1) represented a rare ent-rosane-type diterpenoid with a 5/7/6 skeleton. Euphoainoid G (8) was a rare rosane diterpenic acid. Compounds 9 and 10 carried infrequent tetrahydrofuran rings, and compounds 11-13 was 18-nor-ent-rosane diterpenoids. All isolates were evaluated for their inhibitory effects on RANKL-induced osteoclasts. Notably, compounds with aromatic ester groups (2-7) showed promising activities (IC50 < 10 µM), underscoring the significance of acylated A-ring moieties in the ent-rosane skeleton for anti-osteoclastogenesis. Thirteen synthetic derivatives were obtained through esterification of 17. Of these, compound 27 exhibited remarkable improvement, with an IC50 of 0.8 µM, more than a 12-fold increase in potency compared to the parent compound 17 (IC50 > 10 µM). This work presents a series of new ent-rosane diterpenoids with potential antiosteoporosis agents.

Phytochemical screening, HPLC analysis, antimicrobial and antioxidant effect of Euphorbia parviflora L. (Euphorbiaceae Juss.).

Plant extracts are actively being used worldwide due to the presence of biologically active constituents helping in the preservation of food, and to aid against various diseases owing to their antimicrobial and antioxidant potential. The present research work was carried out to investigate the phytochemical constituents, antimicrobial activity, and antioxidant activity of different extracted samples of Euphorbia parviflora. Anti-microbial studies were carried out by Agar well diffusion while the DPPH method was employed for investigating anti-oxidant activity. Three samples from methanol, chloroform, and ethyl acetate extract were tested against five different bacterial strains comprising two species from Gram-negative bacteria i.e., Staphylococcus aureus and Bacillus subtilis and three species from Gram-positive bacteria i.e. Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia along two fungal strains i.e. Candida albicans and Aspergillus niger. The results of the qualitative phytochemical analysis showed that methanolic, chloroformic, and ethylacetate extract of Euphorbia parviflora consist of alkaloids, reducing sugars, flavonoids, terpenoids, tannins, and saponins. The total phenol and flavonoid content of E. parviflora showed that the methanolic extract of E. parviflora had a significantly higher total phenolic content (53.73 ± 0.30 mg of GAE/g) and flavonoid content (44.62 ± 0.38 mg of than other extracts. The content of total phenolic and flavonoids was more in methanolic extract as compared to other extracts of E. prolifera. The HPLC analysis showed that in the chloroform extract of E. parviflora Cinnamic acid (4.32 ± 2.89 mg/g) was dominant, in methanol extract quercetin (3.42 ± 2.89 mg/g) was dominant and in ethyl acetate extract of E. parviflora catechin (4.44 ± 2.89 mg/g) was found dominant. The antimicrobial activity revealed that amongst all the extracts the highest antibacterial activity was shown by methanolic extract against B. subtilis and Staphylococcus aureus as compared to the other extracts. The antioxidant activity revealed that methanolic extract of E. parviflora demonstrated higher antioxidant activity (82.42 ± 0.02) followed by chloroform extract (76.48 ± 0.08) at 150 µg/mL. The aim of this study was primarily to evaluate the potential of this plant as a reliable source of antimicrobials and antioxidants that may be used for the treatment of various infectious diseases in the future. The study provides evidence that this plant can act as a reliable source of antimicrobial and antioxidant agents and might be used against several infectious diseases.

Enhancing lathyrane structural diversity and MDR activity by combinatorial modification of lathyrane nucleus and ester side chain: A case study of Euphorbia Factor L1 and Euphorbia Factor L3.

The chemical transformation of lathyrane nucleus through reduction and oxidation reactions using Euphorbia Factor L1 (EFL1) and Euphorbia Factor L1 (EFL3) as examples were investigated, along with a co-modification strategy of lathyrane nucleus and its side ester chain. A total of 38 lathyrane derivatives (5-42) including 34 new compounds were obtained, which greatly enriched the structural diversity of the lathyrane-type diterpenoids. Cytotoxicity against drug-sensitive and drug (adriamycin, ADM) resistant MCF-7 cells showed that 23 out of 38 transformed derivatives possessed obvious cytotoxic activity with IC50 values ranging from 7.0 to 41.1 µM and 3.2 to 45.5 µM, respectively, against both cells, compared to the noncytotoxic EFL1 and EFL3. The multidrug resistance (MDR) reversing activities of these lathyrane derivatives were further evaluated in MCF-7/ADM. Three transformed compounds (reversal fold, RF = 151.33, 62.94 and 47.3 for 27, 37 and 42) showed markedly higher activity than EFL1 (RF = 32.92) and EFL3 (RF = 39.68). Structure-activity relationship study revealed an essential role of C-6/17 and C-12/13 double bonds on lathyrane nucleus for exerting MDR reversal activity. Western blotting analysis showed that 42 could reduce the expression level of P-glycoprotein (P-gp) in MCF-7/ADM cells; however, the most active compound 27 with an unnatural 5/7/7/4 fused-ring diterpenoid skeleton, had no inhibitory effect on P-gp expression.

Biochemical characterization of Euphorbia resinifera floral cyathia.

Euphorbia resinifera O. Berg is a plant endemic to the Northern and Central regions of Morocco known since the ancient Roman and Greek times for secreting a poisonous latex containing resiniferatoxin. However, E. resinifera pseudo-inflorescences called cyathia are devoid of laticifers and, therefore, do not secrete latex. Instead, they exudate nectar that local honey bees collect and craft into honey. Honey and cyathium water extracts find a broad range of applications in the traditional medicine of Northern Africa as ointments and water decoctions. Moreover, E. resinifera monofloral honey has received the Protected Geographic Indication certification for its outstanding qualities. Given the relevance of E. resinifera cyathia for bee nutrition, honey production, and the health benefit of cyathium-derived products, this study aimed to screen metabolites synthesized and accumulated in its pseudo-inflorescences. Our analyses revealed that E. resinifera cyathia accumulate primary metabolites in considerable abundance, including hexoses, amino acids and vitamins that honey bees may collect from nectar and craft into honey. Cyathia also synthesize volatile organic compounds of the class of benzenoids and terpenes, which are emitted by flowers pollinated by honey bees and bumblebees. Many specialized metabolites, including carotenoids, flavonoids, and polyamines, were also detected, which, while protecting the reproductive organs against abiotic stresses, also confer antioxidant properties to water decoctions. In conclusion, our analyses revealed that E. resinifera cyathia are a great source of antioxidant molecules and a good food source for the local foraging honeybees, revealing the central role of the flowers from this species in mediating interactions with local pollinators and the conferral of medicinal properties to plant extracts.

Diverse diterpenoids and a triterpenoid from Euphorbia spinidens Bornm. ex Prokh.

Four previously unreported diterpenoids including three ent-atisanes (1-3) and one ent-abietane (4), along with one known linear triterpenoid (5) and five known diterpenoids including four myrsinanes (6-9), and one abietane (10) have been isolated from the roots of Euphorbia spinidens Bornm. ex Prokh. The structures were determined on the basis of extensive spectroscopic analyses including HR-ESI-MS, 1D and 2D NMR and comparison of the data with those reported in the literature. Antimicrobial potential of isolated compounds were also evaluated. Guionianol B (10) showed good antibacterial activity against Staphylococcus aureus and Bacillus subtilis with MIC value of 6.25 µg/mL.

Euphzycopins A - D, macrocyclic diterpenoids with potential anti-inflammatory activity from Euphorbia Helioscopia.

Four new diterpenoids (1-4) and four known diterpenoids (5-8) were purified from the whole plant of Euphorbia helioscopia L. Compounds 1 and 2 were jathophanes diterpenoids with a 5/12 polycyclic systems, compound 3 was rhamofolane diterpenoid with a 5/10 bicyclic skeleton and compound 4 was a rare class of euphorbia diterpenes featuring an unusual 5/10 fused ring system. Anti-inflammatory activity tests were conducted on the separated compounds, indicating that compound 4 had significant inhibitory effect on NLRP3 inflammasome with an IC50 value of 7.75 µM. Further, the inhibitory effect of 4 was determined using immunofluorescence assays.

Medicinal Effects, Phytochemistry, Pharmacology of Euphorbia prostrata and Promising Molecular Mechanisms.

Euphorbiaceae is a large family of dicotyledonous angiosperms with diverse genera including Euphorbia prostrata (E. prostrata). Current research has provided scientific evidence for traditional uses of E. prostrata against diverse pathological conditions such as anti-hemorrhoidal, anti-inflammatory, analgesic, wound healing, antioxidant, antibacterial, leishmanicidal, antitumor activity, and so on. The phytochemical screening has revealed the presence of glycosides, phytosterols, flavonoids, polyphenols, tannins, and anthraquinones with chemical structures elucidation of their respective compounds. The uniqueness of such multifactorial compounds present in this species endorses it as the potent therapeutic or prophylactic choice for several fatal diseases. Although ethnomedical applications served as a significant citation for pharmacology, the molecular mechanism has not been reviewed yet. The present paper provides a comprehensive review of research outcomes, pharmacology, toxicology, and molecular signaling of phytochemicals of E. prostrata species as a reference for relevant researchers. The study of bioactive compounds in crude extracts and fractions, the demonstration of primary mechanisms of pharmacology, along with the addition of toxicity, and clinical trials, should be conceded in depth. This review underlines the E. prostrata species that can be a promising phytomedicine since we are committed to excavating more intensely into their pharmacological role.

A partial peroxisome proliferator-activated receptor gamma agonist isolated from the roots of Euphorbia sikkimensis.

Chemical constituents of the Euphorbia sikkimensis roots was investigated and twelve known compounds were isolated, including three ent-atisane diterpenes: ent-(13S)-hydroxyatis-16-ene-3,14-dione (1), ent-(5ß,8α,9ß,10α,11α,12α)-11-hydroxyatis-16-ene-3,14-dione (2), ent-atisane-3-oxo-16α,17-diol (3); two kaurene diterpenes: ent-kaurane-3-oxo-16α,17-diol (4), ent-kaurane-3-oxo-16ß,17-diol (5); one lathyane diterpene of latilagascene B (6); two flavonoids: quercetin (7), luteolin (8); one lignin d-pinoresinol (9); one coumarin scopoletin (10); together with ethyl gallate (11), p-hydroxybenzaldehyde (12). Their structures were identified based on the extensive spectroscopic analysis in comparison with the literature data. Compounds 1, 2, 4, 6 and 9 were isolated from Euphorbia sikkimensis for the first time. The agonistic activity of peroxisome proliferator-activated receptor gamma (PPARγ) for compounds 1, 7, 8, 9 and 11 was evaluated. Compound 1 exhibited moderate agonistic activity for PPARγ receptor with relative fluorescence intensity of 10.19 at 30.0 µM, in comparison with that of the positive control of rosiglitazone (28.50 at 2.0 µM).

Euphorbia grantii Oliv. standardized extract and its fraction ameliorate doxorubicin-induced cardiomyopathy in Ehrlich carcinoma bearing mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia plants have long been used as traditional medicine in China, Europe, America, Turkey, India, Africa, Iran, and Pakistan because of its high medicinal value and health advantages especially as a remedy for several types of cancer. AIM OF THE STUDY: Doxorubicin (DOX) is one of the most frequently prescribed drugs in cancer chemotherapy, with dose-limiting cardiotoxicity. The development of medicinal approaches to attenuate drug's toxicity represents an area of great concern in cancer research. Because research on this topic is still disputed and limited, we aim to investigate the potential of supplementation with Euphorbia grantii Oliv. on DOX-induced cardiomyopathy in Ehrlich carcinoma bearing mice. MATERIALS AND METHODS: The high-performance thin layer chromatography (HPTLC) analysis of total methanolic extract (TE), and its bioactive dichloromethane fraction (DCMF) was applied for the determination of friedelin. Male BALB/c mice were used to keep the Ehrlich ascites tumor cells. The experiment was performed for a 2-weeks period. RESULTS: A good linearity relationship was found to be with correlation coefficient (r2) value of 0.9924 for the isolated friedelin. Limit of detection (LOD) and limit of quantitation (LOQ) was found to be 0.00179, and 0.000537 ng/band respectively for friedelin. The amount of friedelin in the TE and DCMF were determined by using calibration curve of standard as 106.32 ± 5.69 µg, and 159.2 ± 4.24 µg friedelin/mg extract, respectively. DOX-induced cardiomyopathy by decreasing the ejection fraction (EF) compared to the Ehrlich and negative control groups. It resulted in a decrease in the EF by 30 and 39% compared to the other groups. High and low doses of the TE and DCMF did not result in significantly different ejection fractions compared to the Ehrlich group. Co-administration of DCMF with DOX ameliorated the alteration in the serum CKMB and LDH levels. As revealed from histopathological study, DOX impairs viability of cardiac myocytes and DCMF could effectively and extensively counteract this action of DOX and potentially protect the heart from severe toxicity of DOX. CONCLUSIONS: Finally, our results indicated that Euphorbia grantii Oliv. would be the best option to reduce DOX adverse effects.

Microscopic characterization, TLC fingerprinting and optimization of total lipid content from Euphorbia neriifolia (L.) using response surface methodology.

Euphorbia neriifolia (EN) is a medicinal plant used to treat a variety of ailments in traditional systems. Despite numerous studies on pharmacological activities, no information was available on the microscopic study of this plant. This is the first study that has been attempted to fill this need by performing the light and field emission scanning electron microscopy (FESEM) of leaf, stem, and latex. The powder microscopy of several organs (leaves, stem, and bark) and exudate (latex) of EN was carried out using safranine, fast green, phloroglucinol, and other standard solutions at different magnifications. The chemical fingerprinting of petroleum ether extract was accomplished by using thin layer chromatography. The optimization of total lipid content from the EN leaf under ultrasound-assisted extraction (UAE) and soxhlet extraction (SE) procedure was determined using response surface methodology (RSM). The studied factors that affect the lipid content were: solvent ratio, extraction temperature, and extraction time. Several notable characteristics observed in the leaf of EN are amphistomatic leaves with anticlinical cell walls, anomocytic stomata, spongy mesophyll cells, elongated palisade cells, angular collenchyma, and U-shaped vascular bundle. The plano-convex midrib is covered by polygonal to oval-shaped cuticles and contains anomocytic stomata. The circular petiole has no trichomes and contains laticifers, crystals, and idioblasts. The circular stem was observed with trichomes, hypodermis, collenchyma, parenchymatous cells, central pith, pentagonal stellar region, cambium, and 2-4 times more xylem that of phloem. All of the powdered plant parts and exudate under study contained trichomes, xylem vessels, wood fibers, cork cells, starch grains, calcium oxalate crystals, idioblasts, lignified cork, tannin content, stone cells, and oil globules. The blackish-green colored petroleum ether extract with semi-solid consistency showed the greatest percent (%) yield of 4% in the latex of EN. The thin layer chromatography (TLC) examination of petroleum ether extract of EN leaf produced a maximum 6 spots with Rf values of 0.16, 0.58, 0.62, 0.73, and 0.96 in the mobile phase of petroleum ether-acetone (8:2). In terms of optimization, the dark green colored UAE extract with semi-sticky consistency showed highest % yield of 4.5% whereas the yellowish green colored SE extract of sticky consistency showed the highest % yield of 4.9%. The findings showed that there were not many differences in the total lipid content between UAE (0.16%) and SE (0.11%). However, the best optimum condition for lipid content extraction analysis was obtained as follows: solvent ratio (PE:HE) 50:50, extraction temperature 50°C, extraction time 45 min for UAE, and solvent ratio (PE:HE) 60:40, extraction temperature 45°C, and extraction time of 24 h for SE. Hence, this study signifies the various noteworthy microscopic features along with the presence of different phytocompounds through TLC and best optimized condition for the extraction of lipids from different parts of EN. As no previous study has been reported, the outcomes obtained from the current study prove to be beneficial in the identification of species, quality control, and detection of any adulteration from the laboratory and commercial samples of EN. RESEARCH HIGHLIGHTS: The percent yield was found to be maximum in latex extract (4%). The leaf pet ether extract was separated into 6 bands with different Rf values. The extracted compounds from Euphorbia neriifolia leaves were categorized into non-polar heat tolerant. The highest total lipid yield (0.1119) was obtained at solvent ratios 60:40 of PE:HE (petroleum ether: petroleum hexane).

Metabolomics-based investigation of the chemical composition changes in Mongolian medicinal plant Euphorbia pekinensis before and after processing with Chebulae Fructus.

Euphorbia pekinensis (EP), known for its diuretic properties, is clinically utilized for treating conditions such as edema and malignant tumors. However, in its raw form, Euphorbia pekinensis is toxic, and oral administration of this crude medicine can lead to gastrointestinal stimulation, resulting in abdominal pain and diarrhea. In Mongolian medicine's ethnomedicinal system, a distinctive processing method called "Chebulae Fructus processing" is employed. Chebulae Fructus is used to mitigate the toxicity of EP and alleviate its purgative effects. Nevertheless, the detoxification mechanism associated with this processing method remains unexplored. It is hypothesized that processing with Chebulae Fructus may alter the chemical composition of EP, and the residual components of Chebulae Fructus within processed Chinese medicine might exhibit pharmacological antagonistic effects, thereby achieving the purpose of processing and reducing toxicity. To investigate this further, a combination of UPLC-QTOF-MS-based metabolomics technology and multivariate statistical analysis was employed to analyze and compare the chemical composition of raw and processed EP. Differential variables contributing to group separation were identified based on specific criteria, including VIP (Variable Importance in Projection) values of ≥ 1 in PLS-DA models, p-values < 0.05, and fold changes (FC) > 1.2 or < 0.8. The resulting differentially expressed features were then identified through database matching, literature review, or manual annotation. In total, 47 components were identified from the PEP samples in both positive and negative ionization modes, primarily belonging to flavonoids, terpenoids, organic acids, glycosides, and fatty acids. Among the raw EP group and PEP S4 group, 10 differential compounds were identified. Notably, one toxic terpene and one phenylpropanoid from EP were downregulated, while two bioactive components from Chebulae Fructus were upregulated in the processed group. The possible conversion reactions of these two processing Q-markers were also elucidated. The characteristic processing with Chebulae Fructus resulted in a change in the composition of this Mongolian medicine EP. Furthermore, this study provides a scientific foundation for optimizing the processing technology of EP and offers insights into the processing of other ethnomedicines with toxic properties.

ent-Atisane Diterpenoids from Euphorbia helioscopia and Their Anti-inflammatory Activities.

Phytochemical investigation on the anti-inflammatory fraction extracted from the whole plant of Euphorbia helioscopia L. led to the isolation of three new ent-atisane diterpenoids (1-3) and five known analogues (4-8). The structures and absolute configurations of the new compounds were elucidated by comprehensive analysis of the NMR, MS, IR, ECD, and X-ray crystallography. It is worth mentioning that compound 3 belongs to a rare class of ent-atisane diterpenoid featuring a hydroxyl group at C-9. Bioactivity investigation showed that compounds 4, 7, and 8 exhibited significant inhibitory effects on LPS-induced NO production in a dose-dependent manner, which indicates their anti-inflammatory potential.

Analysis of the mechanism of action of Euphorbia fischeriana Steud on cirrhosis based on network pharmacology.

This study aimed to employ network pharmacology to elucidate the mechanism by which Euphorbia fischeriana Steud (EFS) exhibits the efficacy on cirrhosis. The compounds and targets of EFS were retrieved from Traditional Chinese Medicine Integrated Database and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Next, these compounds and targets were analyzed based on protein-protein interaction (PPI) network. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling network was established based on KEGG database. We constructed a compound-compound target-intersection target-pathway PPI network, including 20 compounds, 19 intersection targets between compound targets and EFS targets. Among the 20 compounds, 8-Isopentenyl-kaempferol has the most targets, with 27 targets, followed by 3,4',5-Trihydroxy-7-methoxy-8-isopentenylflavone, Formononetin, Isoxanthohumol, and Isokurarinone with potential targets of 26, 22, 18, and 14, respectively. Top 5 targets are HSP90AA1, PTGS2, NOS2, MAPK14, and PPARG. KEGG pathway enrichment analysis showed that pathways such as Hepatitis B, Hepatitis C, Lipid and atherosclerosis, and AGE-RAGE signaling pathway in diabetic complications were closely related to the infection and abnormal metabolism of the liver. The application of network pharmacology could identify potential targets of EFS with a low false-positive rate and provide novel insight into the mechanism of action of EFS on cirrhosis.

In vitro anthelmintic activity of Euphorbia forskalii J. Gay aqueous extracts evaluation on different life stages of Haemonchus contortus.

The use of medicinal plants in the control of gastrointestinal parasitosis is a promising solution for improving the productivity of sheep flocks. In order to evaluate the anthelmintic activity of Euphorbia forskallii, in vitro bioassays were performed on three life stages of Haemonchus contortus. Five aqueous extracts concentrations namely 10 mg/mL; 5 mg/mL; 2.5 mg/mL; 1.25 mg/mL and 0.62 mg/mL were used for adult worm mortality tests. Egg hatch inhibition and L3 larval migration inhibition tests were studied at 5 mg/mL; 2.5 mg/mL; 1.25 mg/mL; 0.62 mg/mL and 0.31 mg/mL. A negative control PBS and a positive control levamisole 2.5 mg/mL were established for each test. A phytochemical screening was performed to determine the presence of some secondary metabolites. The results obtained showed the presence of total polyphenols, total flavonoids and condensed tannins within the aqueous extracts of E. forskalii. A high and significant (P < 0.05) morality rate compared to the negative control with an LC50 of 2.30 mg/mL was obtained. Inhibition of egg hatch and larval migration were high and significant (p < 0.05) compared to the negative control. There was an IC50 of 1.03 mg/mL and 0.92 mg/mL respectively for inhibition of egg hatching and L3 larval migration. The present study revealed the in vitro anthelmintic activity of E. forskalii aqueous extracts and allows us to consider in perspective complementary studies to confirm this activity.

Phytochemical Analysis, Antioxidant Activities In Vitro and In Vivo, and Theoretical Calculation of Different Extracts of Euphorbia fischeriana.

Euphorbia fischeriana has a long-standing history of use in traditional medicine for the treatment of tuberculosis diseases. However, the plant's therapeutic potential extends beyond this specific ailment. The present study aimed to investigate the antioxidant properties of Euphorbia fischeriana and lay the groundwork for further research on its potential therapeutic applications. Phytochemical tests were performed on the plant, and 11 types of phytochemicals were identified. Ultraviolet-visible spectrophotometry was used to evaluate the active components and antioxidant properties of eight different solvent extracts, ultimately selecting acetone extract for further research. UHPLC-ESI-Q-TOF-MS identified 43 compounds in the acetone extract, and chemical calculations were used to isolate those with high content and antioxidant activity. Three stability experiments confirmed the extract's stability, while cell viability and oral acute toxicity studies demonstrated its relatively low toxicity. In rats, the acetone extract showed significant protective effects against D-galactosamine-induced liver damage through histopathological examination and biochemical analysis. These results suggest that Euphorbia fischeriana's acetone extract has potential in treating diseases related to oxidative imbalances. Therefore, this study highlights the plant's potential therapeutic applications while providing insight into its antioxidant properties.

Euphopias G - J, macrocyclic diterpenes with anti-zika virus activity from Euphorbia helioscopia L.

Four new diterpenoids (1-4) and sixteen known diterpenoids (5-20) were purified from the whole plant of Euphorbia helioscopia L. Compounds 1 and 2 were rhamofolane diterpenoids with a 5/7/6 tricyclic systems, compound 3 was a lathyranes diterpenoid, and compound 4 was a jathophanes diterpenoid. The isolated compounds were tested for their cytotoxicity and anti-Zika virus properties, and compounds 9 and 15 showed low cytotoxicity and strong anti-Zika virus properties with EC50 2.63 and 5.94 µM, respectively. Further, the inhibitory effects of compounds on protein levels were determined using Western blotting and immunofluorescence assays.

Yuexiandajisu diterpenoids from Euphorbia ebracteolata Hayata (Langdu roots): An overview.

The roots of the plant Euphorbia ebracteolata Hayata (Yue Xian Da Ji) are commonly used in traditional Chinese medicine to treat multiple diseases such as chronic liver diseases, oedema, pulmonary diseases and cancer. It is the main ingredient of the TCM called Langdu which can be prepared also from roots of E. fischeriana Steud. and occasionally from Stellera chamaejasme species. Numerous bioactive natural products have been isolated from E. ebracteolata including a large diversity of diterpenoids with anti-inflammatory and anticancer properties. One little series of compounds has been named yuexiandajisu (A, B, C, D, D1, E, F) which comprises two casbane-, one isopimarane-, two abietane-, and two rosane-type diterpenes including a dimeric molecule. The origin, structural diversity and properties of these little-known natural products is discussed here. Several of these compounds have been identified in the roots of other Euphorbia species, notably the potent phytotoxic agent yuexiandajisu C. The abietane diterpenes yuexiandajisu D-E exhibit marked anticancer properties but their mechanism of action remains unresolved. The dimeric compound, renamed yuexiandajisu D1, also exhibit anti-proliferative properties against cancer cell lines, unlike the rosane diterpene yuexiandajisu F. The structural or functional analogy with other diterpenoids is discussed.

Ganodermasides E-H, four new ergosterol derivatives from the endophytic fungus Epicoccum poae DJ-F associated with Euphorbia royleana.

Ganodermasides E-H (1-4), four new ergosterol derivatives and two known ones (5 and 6) were isolated from the fermentation of the endophytic fungus Epicoccum poae DJ-F in the stems of Euphorbia royleana Boiss. Their structures were elucidated by spectroscopic analysis, including extensive 1D NMR, 2D NMR, and HRESIMS techniques. All the isolated compounds were tested for their vitro antibacterial activity. Compounds 1-6 showed weak inhibitory effects on Staphylococcus epidermidis, Pseudomonas syringae, and Ralstonia solanacearum with MIC values ranging from 0.4 to 3.6 mM.

[Optimization of parameters for stir-frying of Kansui Radix with vinegar based on conversion of toxic components].

This study aims to optimize the parameters for stir-frying of Kansui Radix with vinegar based on the conversion of representative toxic diterpenes, which is expected to serve as a reference for the standardized production of Kansui Radix stir-fried with vinegar. To be specific, the toxic components [3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol(3-O-EZ), kansuiphorin C(KPC)] in Kansui Radix and the products(ingenol, 20-deoxyingenol) after the stir-frying with vinegar were selected. The toxicity to intestine and water-draining activity were evaluated with NCM460(normal human colon mucosal epithelial cell line) and HT-29(a human colorectal adenocarcinoma cell line). An HPLC method was then developed to assess the conversion of toxic components. On this basis, temperature, time, and amount of vinegar for the processing of Kansui Radix were optimized with the Box-Behnken design and the content of ingenol and 20-deoxyingenol as evaluation index. The results showed that after the stir-frying of Kansui Radix with vinegar, 3-O-EZ and KPC were first converted to monoester 3-O-(2'E,4'Z-decadienoyl)ingenol(3-EZ) and 5-O-benzoyl-20-deoxyingenol(5-O-Ben) and finally to almost non-toxic ingenol and 20-deoxyingenol, respectively. Meanwhile, the water-draining activity was retained. Six compounds had a good linear relationship with the peak area in the corresponding concentration ranges(R~2≥0.999 8), and the average recovery fell in the range of 98.20%-102.3%(RSD≤2.4%). The content of representative diterpenes and intermediate products was 14.78%-24.67% lower in the Kansui Radix stir-fried with vinegar than in the Kansui Radix, while the content of the conversed products was 14.37%-71.37% higher. Among the process parameters, temperature had significant influence on the total content of products, followed by time. The optimal parameters were 210 ℃, 15 min, and 30% vinegar. The relative error between the experimental results and the predicted values was 1.68%, indicating that the process was stable and reproducible. The strategy of screening optimal parameters for stir-frying of Kansui Radix with vinegar based on the transformation of toxic components can help improve the production stability, reduce the toxicity, and ensure the efficacy of Kansui Radix stir-fried with vinegar, which can serve as a reference for the process optimization of similar toxic Chinese medicinals.

Network pharmacology and molecular docking combined with widely targeted metabolomics to elucidate the potential compounds and targets of Euphorbia helioscopia seeds for the treatment of pulmonary fibrosis.

BACKGROUND: The whole herb of Euphorbia helioscopia has been traditionally used for treating pulmonary tuberculosis, malaria, warts, lung cancer and bacillary dysentery for a long time in China. However, E. helioscopia seeds are often discarded and its medicinal value is often ignored, resulting in a waste of resources. METHOD: In this work, widely targeted metabolomics based on UPLC-ESI-QTRAP-MS/MS methods and metware database (MWDB) were firstly used to identify the chemical compositions of EHS. Besides, network pharmacology, molecular docking and molecular dynamics simulation were performed for elucidating the potential compounds and targets of E. helioscopia seeds for the treatment of pulmonary fibrosis via common database (like TCMSP, Genecards, DAVID, STRING) and common software (like Sybyl, Cytoscape, Pymol and Schrödinger). RESULT: The results of widely targeted metabolomics showed 231 compounds including 12 categories were identified. The highest content compositions are lipids (33.89%) followed by amino acids and derivatives (21.78%), nucleotides and derivatives (15.73%), as well as the content of functional ingredients like phenolic acids (7.33%), alkaloids (7.03%) and flavonoids (4.51%) are relatively high. Besides, the results of network pharmacology and molecular docking showed that EHS presented anti-pulmonary fibrosis medicinal value through multi-ingredients, multi-targets and multi-pathways approach. Key ingredients including 9-Hydroxy-12-oxo-15(Z)-octadecenoic acid, Nordihydrocapsiate, 1-O-Salicyl-d-glucose, 9-(Arabinosyl)hypoxanthine, Xanthosine and Galangin-7-O-glucoside. Key targets including SRC, HSP90AA1, AKT1, EGFR, JUN, EP300 and VEGFA, and key signaling pathways mainly related to AGE-RAGE, EGFR tyrosine kinase inhibitor resistance, VEGF and HIF-1 signaling pathway. Molecular dynamics simulation showed that HSP90AA1 and 9-Hydroxy-12-oxo-15(Z)-octadecenoic complex (with the highest docking score) have a stable combination effect. CONCLUSION: In conclusion, this study revealed the chemical compositions of EHS and its anti-pulmonary fibrosis medicinal effect for the first time, it will provide scientific insight for the development of EHS as medicinal resource.