Anti-inflammatory, healing and antiophidic potential of Jatropha mollissima (Pohl) Baill. (Euphorbiaceae): From popular use to pharmaceutical formulation in gel.

Jatropha mollissima (Pohl) Baill. (Euphorbiaceae) is widely used in traditional medicine to treat inflammatory disorders. So, a topical gel containing the hydroethanolic extract of its leaves was developed and evaluated for its anti-inflammatory, wound healing, and antiophidic properties in mice. First, the chemical profile of different parts of the plant was characterized by liquid chromatography coupled to mass spectrometry (LC-MS) using molecular networking. In the leaf extract, 11 compounds were characterized, with a particular emphasis on the identification of flavonoids. The gel efficiently inhibited carrageenan-induced paw edema, as well as acute and chronic croton oil-induced ear edema models, thereby reducing inflammatory and oxidative parameters in inflamed tissues. Besides anti-inflammatory activity, the herbal gel showed significant wound healing activity. The edematogenic, hemorrhagic and dermonecrotic activities induced by Bothrops jararaca snake venom were effectively inhibited by the treatment with J. mollissima gel. The association with the herbal gel improved in up to 90% the efficacy of commercial snake antivenom in reduce venom-induced edema. Additionally, while antivenom was not able to inhibit venom-induced dermonecrosis, treatment with herbal gel reduced in 55% the dermonocrotic halo produced. These results demonstrate the pharmacological potential of the herbal gel containing J. mollissima extract, which could be a strong candidate for the development of herbal products that can be used to complement the current antivenom therapy against snake venom local toxicity.

Sacha Inchi: The Promising Source of Functional Oil for Anti-Aging Product.

Sacha inchi (Plukenetia volubilis) oil is constituted with macronutrients and the health benefit fatty acids. In this context, the efficient of Sacha inchi oil for anti-aging product is presented. The light-clear yellowish seed oil of Sacha inchi was revealed on its physicochemical properties that are in the same range of the commercializing plant-oil supplied for topical products. The oil was GC/MS exhibited to be constituted with α-linolenic (51.72%) and linoleic (24.3%) acids, with unsaturated/saturated fatty acids ratio of 21.26. The oil was noted onto its potent in vitro antioxidant activity assessed by ABTS, DPPH and FRAP assays. In addition, the oil (1-3%) was proved to be safe in normal human fibroblast cells. Furthermore, the oil exhibited cellular antioxidant with inhibitory effect against MMP-2. Sacha inchi oil is therefore highlighted as a potential source of nutraceutical especially for anti-aging product. The oil is specified for the product development in terms of physicochemical, chemical and biological profiles. Innovative processing of Sacha inchi is therefore encouraged as the promising plant for anti-aging product.

Potential hemostatic compounds targeting urokinase plasminogen activator explored from three Euphorbiaceae species: Euphorbia maculata, Euphorbia humifusa, and Acalypha australis, with bio-affinity ultrafiltration UPLC-MS.

INTRODUCTION: Numerous species of the Euphorbiaceae family, including Euphorbia maculata, Euphorbia humifusa, and Acalypha australis, have been used to manage bleeding disorders. However, few investigations have demonstrated their hemostatic potential, and their procoagulant compounds remain elusive. OBJECTIVE: This study aimed to determine the most active procoagulant extracts from the three species' crude extract (CE) and fractions in order to screen out the active compounds and to analyze their possible mechanisms of action. METHODS: An integrative approach, comprising prothrombin time and activated partial thromboplastin time evaluations and urokinase-type plasminogen activator (uPA) inhibitory assessment, followed by bio-affinity ultrafiltration paired with UPLC/QTOF-MS targeting uPA and docking simulations, was used. RESULTS: The extracts with highest procoagulant activity were the CE for both E. maculata (EMCE) and E. humifusa (EHCE) and the n-butanol fraction (NB) for A. australis (AANB). The most promising ligands, namely, isoquercetin, orientin, rutin, and brevifolin carboxylic acid, were selected from these lead extracts. All of these compounds exhibited pronounced specific binding values to the uPA target and showed tight intercalation with the crucial side chains forming the uPA active pocket, which may explain their mode of action. The activity validation substantiated their hemostatic effectivity in inhibiting uPA as they had better inhibition constant (Ki) values than the reference drug tranexamic acid. CONCLUSION: Collectively, the integrative strategy applied to these three species allowed the elucidation of the mechanisms underlying their therapeutic effects on bleeding disorders, resulting in the fast detection of four potential hemostatic compounds and their mode of action.

Unveiling the anti-inflammatory potential of Acalypha indica L. and analyzing its research trend: digging deep to learn deep.

The plant Acalypha indica L. is a well-known traditional plant belonging to the family Euphorbiaceae. Traditional practices of the plant claim to treat asthma, pneumonia, wound healing, rheumatoid arthritis, bronchitis, and skin disorders. The major phytochemicals reported are cyanogenic glucosides, tannins, coumarins, flavonoid glycosides, fatty acids, and volatile oils. To summarize the anti-inflammatory potential of Acalypha indica extract and its phytochemicals through preclinical studies. The search terms include anti-inflammatory, Acalypha indica, and Acalypha indica extract independently or in combination with pro-inflammatory markers using various databases, including Scopus, Web of Science, PubMed, ProQuest, and Google Scholar. The results of preclinical studies confirm that Acalypha indica exhibits strong anti-inflammatory activity. Most of the experimental studies that have been conducted on plant extract are protein denaturation, human red blood cell membrane stabilization assay, and carrageenan-induced inflammation models. However, the molecular mechanism in these studies is still unclear to demonstrate its anti-inflammatory effects. Acalypha indica possesses anti-inflammatory effects that may be due to the presence of phenolic compounds especially flavonoids present in the Acalypha indica. Thus, further research is needed, to understand mechanistic insights of the plant phytochemicals to represent anti-inflammatory properties.

Strophioblachins A-K, Structurally Intriguing Diterpenoids from Strophioblachia fimbricalyx with Potential Anticardiac Hypertrophic Inhibitory Activity.

Three new rearranged diterpenoids, strophioblachins A-C (1-3), eight new diterpenoids, strophioblachins D-K (4-11), and seven previously described diterpenoids (12-18) were purified from the aerial parts of Strophioblachia fimbricalyx. Compounds 1 and 2 contain a rare 6/6/5/6 ring system, while 3 has an uncommon tricyclo[4.4.0.08,9]tridecane-bridged unit, and their diterpenoid skeletons are being reported for the first time. Utilizing spectroscopic and HRESIMS data analysis, the structures of the new compounds (1-11) were established, and ECD and 13C NMR calculations were used to confirm the relative and absolute configurations of 11 and 9. The absolute configurations of compounds 1, 3, and 10 were established using single-crystal X-ray diffraction. The results of testing for anticardiac hypertrophic activity demonstrated that compounds 10 and 15 dose-dependently lowered the mRNA expression of Nppa and Nppb. Protein levels were confirmed by Western blotting, which also demonstrated that compounds 10 and 15 lowered the expression of the hypertrophic marker ANP. The cytotoxic activity against neonatal rat cardiomyocytes was assayed in vitro by the CCK-8 and ELISA methods, and the results showed that compounds 10 and 15 were only very weakly active in the range.

Strophiofimbrins A and B: Two Rearranged Norditerpenoids with Novel Tricyclic Carbon Skeletons from Strophioblachia fimbricalyx.

Two rearranged norditerpenoids with novel tricyclic carbon skeletons, strophiofimbrin A (1) and strophiofimbrin B (2), were isolated from Strophioblachia fimbricalyx. Their structures were established by 1D/2D NMR spectroscopy, HRESIMS, quantum chemistry calculations, and X-ray diffraction analyses. 1 and 2 represented the first examples of diterpenoids with unprecedented 5/6/7-fused ring systems. In the proposed biosynthetic pathway, they were suspected to derive from cleistanthane norditerpenoids via ring opening, expansion, cyclization, and rearrangement based on the existence of phenanthrenone and cleistanthane diterpenoids from Strophioblachia and Trigonostemon, two closely related genera of the Euphorbiaceae family. Furthermore, compounds 1 and 2 exhibited significant proliferation inhibition and obvious neuroprotective effects.

An overview of the traditional use, phytochemistry, and biological activity of the genus Homalanthus.

Homalanthus species are native to tropical Asia and the Pacific region. This genus, comprising 23 accepted species, received less scientific attention compared to other genera of the Euphorbiaceae family. Seven Homalanthus species, such as H. giganteus, H. macradenius, H. nutans, H. nervosus, N. novoguineensis, H. populneus, and H. populifolius, have been reported to treat various health problems in traditional medicine. Only a few Homalanthus species have been investigated for their biological activities, including antibacterial, anti-HIV, anti-protozoal, estrogenic, and wound-healing activities. From a phytochemical point of view ent-atisane, ent-kaurane, and tigliane diterpenoids, triterpenoids, coumarins, and flavonol glycosides were found to be characteristic metabolites of the genus. The most promising compound is prostratin, isolated from H. nutans, with anti-HIV activity and the ability to eradicate the HIV reservoir in infected patients by mechanism of protein kinase C (PKC) agonist. This review provides information on traditional usage, phytochemistry, and biological activity of the genus Homalanthus with the aim to delineate future research directions.

Discovery, disassembly, depolymerization and derivatization of catechyl lignin in Chinese tallow seed coats.

The search for feedstock of catechyl lignin (C-lignin) is great interest and importance, as C-lignin featuring homogeneity and linearity is considered as an "ideal lignin" archetype for valorization and exits in only a few plant seed coats. In this study, naturally occurring C-lignin is first discovered in the seed coats of Chinese tallow, which has the highest content of C-lignin (15.4 wt%) as compared with other known feedstocks. An optimized extraction procedure by ternary deep eutectic solvents (DESs) enables the complete disassembly of C-lignin and G/S-lignin coexisted in Chinese tallow seed coats, and characterizations revealed that the as-separated C-lignin sample is abundant in benzodioxane units with no observation of ß-O-4 structures from G/S-lignin. Catalytic depolymerization of C-lignin results in a simplex catechol product in 129 mg per gram seed coats, being higher than other reported feedstocks. Derivatizing the "black" C-lignin via the nucleophilic isocyanation of benzodioxane γ-OH leads to a "whitened C-lignin" with uniform laminar structure and excellent crystallization ability, being conducive to fabricating functional materials. Overall, this contribution showed that Chinses tallow seed coats are suitable feedstock for acquiring C-lignin biopolymer.

Unique guanidine-conjugated catechins from the leaves of Alchornea rugosa and their autophagy modulating activity.

Natural guanidines, molecules that contain the guanidine moiety, are structurally unique and often exhibit potent biological activities. A phytochemical investigation of the leaves of Alchornea rugosa (Lour.) Müll.Arg. by MS/MS-based molecular networking revealed eight undescribed guanidine-flavanol conjugates named rugonines A-H. The chemical structures of the isolated compounds were comprehensively elucidated by NMR spectroscopy, HRESIMS, and circular dichroism (CD) analysis. All isolated compounds were tested for autophagosome formation in HEK293 cells stably expressing GFP-LC3. The results revealed that compounds rugonines D-G showed potential autophagy inhibitory activity.

Tragia plukenetii-Assisted Omega-Decenol as Potential Anticancer Agent: its Isolation, Characterization, and Validation.

The second most common and lethal disease is lung cancer. To combat the negative effects of today's synthetic medications, natural phytomedicines are required. Tragia plukenetii is a medicinal plant native to India that belongs to the Euphorbiaceae family. The purpose of this research is to isolate bioactive compounds from T. plukenetii leaves and then test them for anticancer property. A single compound (CH: ME-20:80) was separated using TLC, and an RF value of 0.55 was determined. Spectral analyses utilizing UV-Visible Spectrophotometer and FT-IR were used to examine the absorbance and functional groups. 13C-NMR and 1H-NMR studies revealed the tentative name of the purified phytochemical as omega-decenol (OD). Further antioxidant and anticancer properties of OD were tested for in vitro. In comparison to conventional L-ascorbic acid, the DPPH radical scavenging assay experiment yielded an IC50 of 147.48 g/ml. With an IC50 value of 24 µg/ml (Omega-decenol) and 32 µg/ml (doxorubicin), the MTT assay demonstrated the cytotoxic capability against the A549 lung cancer cell line. FACS revealed the cell cycle arrest of A549 at S phase compared to control with the high-dose IC50 (250 µg/ml) of omega-decenol. Twelve major compounds were detected in the active fraction using GC-MS analysis, where n-hexadecanoic acid was found as a major. Omega-decenol showed good binding affinity against EGFR, amongst other receptors in the in silico docking study. This research reveals the potent anticancer activity of the isolated compound omega-decenol from T. plukenetii leaves and provides a key path to understanding the molecular interaction in anticancer aspects against adenocarcinoma.

Polyoxygenated Terpenoids and Polyketides from the Roots of Flueggea virosa and Their Inhibitory Effect against SARS-CoV-2-Induced Inflammation.

Six new polyoxygenated terpenoids, podovirosanes A-F (1-6), and two known polyketides (7 and 8) were isolated from the roots of F. virosa. Their structures, along with absolute configurations, were deduced using spectroscopic analysis as well as computational calculations, including TDDFT calculation of ECD spectra and GIAO NMR calculations combined with DP4+ probability analysis. Compounds 2, 3, 5, and 8 were found to reduce the phosphorylation levels of NF-κB p65 in SARS-CoV-2 pseudovirus-stimulated PMA-differentiated THP-1 cells.

Tigliane-Type Diterpene Esters from the Fruits of Shirakiopsis indica and Their Anti-HIV Activity.

Four new diterpene esters, shirakindicans A-D (1-4), along with eight related known diterpene esters (5-12), were isolated from the fruits of the Bangladeshi medicinal plant Shirakiopsis indica. The structures of 1-4 were elucidated by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Shirakindican A (1) was assigned as a tigliane-type diterpene ester possessing an unusual 6ß-hydroxy-1,7-dien-3-one structure, while shirakindican B (2) exhibits a tiglia-1,5-dien-3,7-dione structure. The anti-HIV activities of the isolated diterpene esters were evaluated and showed significant activities for sapintoxins A (5) and D (11), with EC50 values of 0.0074 and 0.044 µM, respectively, and TI values of 1 100 and 5 290. Sapatoxin A (12) also exhibited anti-HIV activity with an EC50 value of 0.13 µM and a TI value of 161.

Modification of the Nutritional Quality and Oxidative Stability of Lupin (Lupinus mutabilis Sweet) and Sacha Inchi (Plukenetia volubilis L.) Oil Blends.

Andean lupin (Lupinus mutabilis) oil is rich in monounsaturated (54.2%) and polyunsaturated (28.5%) fatty acids but has a ω-3:ω-6 ratio (1:9.2) above the recommended values for human health. Sacha inchi (Plukenetia volubilis) oil presents a high polyunsaturated fatty acid content (linolenic 47.2% and linoleic 34.7%), along a ω-3:ω-6 ratio (1:0.74) good for human consumption. The objective of this research was to study the physico-chemical properties and oxidative stability of tarwi and sacha inchi oil blends (1:4, 1:3, 1:1, 3:1 and 4:1 w:w) with suitable ω-3:ω-6 ratios. All blends showed ω-3:ω-6 ratios between 1:0.8 and 1:1.9, acceptable from a nutritional point of view, and high total tocopherols' content (1834-688 mg/kg), thanks to sacha inchi. The oxidative stability index (OSI) of the mixtures by the Rancimat method at 120 °C ranged from 0.46 to 8.80 h. The shelf-life of 1:1 tarwi/sacha inchi oil blend was 1.26 years; its entropy (-17.43 J/mol), enthalpy (107.04 kJ/mol), activation energy (110.24 kJ/mol) and Gibbs energy (113.76 kJ/mol) suggest low oxidation reaction rates and good stability. Hence, balanced blends of tarwi/sacha inchi oils can achieve optimal nutritional properties and enhanced shelf-life.

Diterpenoids from Strophioblachia glandulosa and Their NLRP3 Inflammasome Inhibitory Effects.

Our study on the roots and leaves of the never-hitherto-chemically studied S. glandulosa led to the isolation of five new diterpenes, referred to as stroglandulons A-E (1-5), alongside 18 known constituents (6-23). The structures of the new compounds were elucidated on the basis of their spectroscopic data, while the known ones were determined based on the comparison of their data with the literature values. Compounds 1-5 were evaluated for their inhibitory effects against NLRP3 inflammasome activation; compound 5 showed inhibition by an IC50 value of 6.12±0.03 µM.

Ten new prenylated flavonoids from Macaranga denticulata and their antitumor activities.

Ten new prenylated flavonoids, named denticulains A-J (1-10), together with seven known prenylated flavonoids (11-17) were isolated from Macaranga denticulata. Their structures were elucidated on the basis of detailed spectroscopic analysis and by comparison with literature data. In addition, compounds 1 and 14 inhibited the proliferation of SW620 and HCT-116 cell lines with an IC50 value of 46.08 µM and 56.83 µM, respectively.

Identification of Gene Biomarkers for Tigilanol Tiglate Content in Fontainea picrosperma.

Tigilanol tiglate (EBC-46) is a small-molecule natural product under development for the treatment of cancers in humans and companion animals. The drug is currently produced by purification from the Australian rainforest tree Fontainea picrosperma (Euphorbiaceae). As part of a selective-breeding program to increase EBC-46 yield from F. picrosperma plantations, we investigated potential gene biomarkers associated with biosynthesis of EBC-46. Initially, we identified individual plants that were either high (>0.039%) or low EBC-46 (<0.008%) producers, then assessed their differentially expressed genes within the leaves and roots of these two groups by quantitative RNA sequencing. Compared to low EBC-46 producers, high-EBC-46-producing plants were found to have 145 upregulated genes and 101 downregulated genes in leaves and 53 upregulated genes and 82 downregulated genes in roots. Most of these genes were functionally associated with defence, transport, and biosynthesis. Genes identified as expressed exclusively in either the high or low EBC-46-producing plants were further validated by quantitative PCR, showing that cytochrome P450 94C1 in leaves and early response dehydration 7.1 and 2-alkenal reductase in roots were consistently and significantly upregulated in high-EBC-46 producers. In summary, this study has identified biomarker genes that may be used in the selective breeding of F. picrosperma.

Extraction and Fractionation of Prokinetic Phytochemicals from Chrozophora tinctoria and Their Bioactivities.

Chrozophora tinctoria is an annual plant of the family Euphorbiaceae, traditionally used as a laxative, a cathartic and an emetic. A methanolic extract of Chrozophora tinctoria (MEC) whole plant and an n-butanol fraction of Chrozophora tinctoria (NBFC) were analyzed by gas chromatography-mass spectrometry (GC-MS) to detect the phytochemicals. MEC and NBFC were tested for in vitro anti acetylcholinesterase (AChE) potential. The effect of both samples on intestinal propulsive movement and spasmolytic activity in the gastrointestinal tract (GIT) was also studied. About twelve compounds in MEC and three compounds in NBFC were tentatively identified through GC-MS. Some of them are compounds with known therapeutic activity, such as toluene; imipramine; undecane; 14-methyl-pentadecanoic acid methyl ester; and hexadecanoic acid. Both NBFC and MEC samples were checked for acute toxicity and were found to be highly toxic in a dose-dependent manner, causing diarrhea and emesis at 1 g/kg concentration in pigeons, with the highest lethargy and mortality above 3 g/kg. Both the samples of Chrozophora tinctoria revealed significant (p ≤ 0.01) laxative activity against metronidazole (7 mg/kg) and loperamide hydrochloride (4 mg/kg)-induced constipation. NBFC (81.18 ± 2.5%) and MEC (68.28 ± 2.4%) significantly increased charcoal meal intestinal transit compared to distal water (41.15 ± 4.3%). NBFC exhibited a significant relaxant effect (EC50 = 3.40 ± 0.20 mg/mL) in spontaneous rabbit jejunum as compared to MEC (EC50 = 4.34 ± 0.68 mg/kg). Similarly, the impact of NBFC on KCl-induced contraction was more significant than that of MEC (EC50 values of 7.22 ± 0.06 mg/mL and 7.47 ± 0.57 mg/mL, respectively). The present study scientifically validates the folk use of Chrozophora tinctoria in the management of gastrointestinal diseases such as constipation. Further work is needed to isolate the phytochemicals that act as diarrheal agents in Chrozophora tinctoria.

Chemical constituents of Antidesma bunius aerial parts and the anti-AGEs activity of selected compounds.

Thirty-three natural products were isolated from the aerial parts of Antidesma bunius, Euphorbiaceae, a plant used in Vietnamese traditional medicine against rheumatoid arthritis. All compounds were reported the first time for this species, and nine constituents resembled undescribed natural products, noticeably three coumarinolignans with 2,2-dimethyl-1,3-dioxolane moiety, two cyclopeptides, and two furofuran-type lignans connected with a phenylpropanoid moiety. The individual structures were elucidated by combining NMR and MS data, and their configuration was established by NOESY and ECD experiments and NMR calculations. Compounds with sufficient amount were analyzed for their inhibition of advanced glycation endproducts (AGEs) formation, metabolites involved in many diseases like Alzheimer, joint diseases or diabetes. With IC50 values below 0.2 mM rutin and p-hydroxyphenethyl trans-ferulate showed to be moderately active, both still being 10-times more active than the positive control aminoguanidine.

Conglomeratin: a new antibacterial flavonol derivative from Macaranga conglomerata Brenan (Euphorbiaceae).

A new prenylated kaempferol, conglomeratin (1), alongside 7 known compounds including flavonoids (2 and 3), ellagic acid derivatives (4 and 5), triterpenoids (6 and 7), and a coumarin (8) were isolated from the leaves (1 - 5) and stem bark (6 - 8) of Macaranga conglomerata. Their structures were elucidated using spectroscopic and spectrometric techniques. The antibacterial assay was performed using disc diffusion method against Gram-positive and Gram-negative microorganisms. Compound 1 was significantly active against Pseudomonas aeruginosa ATCC 27853 (MIC = 7.8 µg/mL) and moderately active towards Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 31488 (MIC = 62.5 µg/mL). Compound 2 showed potency against P. aeruginosa ATCC 27853 (MIC = 1.0 µg/mL) while 4 and 7 were selective towards K. pneumoniae ATCC 31488 (MIC = 7.8 and 1.0 µg/mL, respectively). These findings suggest that prenylation of flavonoids may contribute to improving their broad-spectrum antimicrobial activities.

Prokinetic and Laxative Effects of Chrozophora tinctoria Whole Plant Extract.

Chrozophora tinctoria (Euphorbiaceae) has been used as an emetic, anthelminthic, and cathartic agent in traditional medicine. We used gas chromatography-mass spectrometry (GC-MS) to characterize the composition of ethyl acetate (EAC) and dichloromethane (DCMC) fractions from the whole Chrozophora tinctoria plant. EAC and DCMC fractions were evaluated for acetylcholinesterase (AChE) inhibitory activity and acute toxicity. Their effects on intestinal propulsive movement and spasmogenic activity of the gastrointestinal tract (GIT) muscle were also assessed. The compounds detected in both fractions were mostly fatty acids, with about seven compounds in EAC and 10 in DCMC. These included pharmacologically active compounds such as imipramine, used to treat depression, or hexadecanoic acid methyl ester, an antioxidant. Both EAC and DCMC fractions inhibited acetylcholinesterase (AChE) activity with IC50 values of 10 µg and 130 µg, respectively. Both the fractions were found to be toxic in a dose-dependent manner, inducing emesis at 0.5 g or higher and lethargy and mortality from 3-5 g upwards. Similarly, both of the fractions showed laxative activity in metronidazole- and loperamide-induced constipation models. EAC relaxed the intestinal muscle at a lower dose (1 mg/mL) than DCMC. Similarly, the EAC extract showed a significant relaxation effect (EC50 = 0.67 ± 0.15 mg/mL) on KCL-induced contraction in rabbit jejunum as compared to DCMC (EC50 = 5.04 ± 0.05 mg/kg). The present study strongly supports the folklore that this valuable plant is a cathartic agent. Further work is required to isolate and validate the bioactive compounds that act as diarrheal agents in Chrozophora tinctoria.