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Journal of Ethnopharmacology Nov 2022Euphorbia is one of the major genera in angiosperms, which is widely distributed all over the world, including Asia, Africa and Central and South America. The roots or... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Euphorbia is one of the major genera in angiosperms, which is widely distributed all over the world, including Asia, Africa and Central and South America. The roots or tubers of Euphorbia are famous for medicinal purposes, especially in China. Many of them, such as Euphorbia pekinensis Rupr, Euphorbia fischeriana Steud and Euphorbia Kansui S.L.Liou ex S.B.Ho. . are used as Chinese herbal medicines.
AIM OF THE STUDY
This paper reviews the diterpenoids isolated from the genus Euphorbia species and the pharmacological activities of these compounds to evaluate its traditional use and potential future development.
MATERIALS AND METHODS
Information on the studies of the genus Euphorbia Linn was collected from scientific journals, books and reports via library and electronic data search (Scifinder, Web of Science, PubMed, Elsevier, Scopus, Google Scholar, Springer, Science Direct, Wiley, ACS, CNKI and Kew Plants of the Word Online). Meanwhile, it was also obtained from published works of material medica, folk records, ethnophmacological literatures, Ph.D. and Masters dissertations.
RESULTS
Known as the main constituents of the genus Euphorbia Linn, Diterpenoids possess many pharmacological properties such as anti-inflammation, antiviral activities and cytotoxicity. To date, various types of diterpenoids were identified from this genus, including isopimarane, rosane, abietane, ent-kaurane, ent-atisane. cembrane, casbane, lathyrane, myrsinane, jatropholane, tigliane, ingenane, jatrophane, paraliane, pepluane, and euphoractin.
CONCLUSIONS
This review describes 14 types of diterpenoid isolated from 45 Euphorbia species from 2012 to 2021, a total of 615 compounds. Among them, mainly include jatrophane (171), lathyrane (92), myrsinane (62), abietane (70), ent-atisane (36), ent-kaurane (7), tigliane (26) and ingenane (19). The possible biological pathways of these compounds were presumed. At the same time, more than 10 biological activities of these compounds were summarized, such as anti-inflammation, antiviral activities and cytotoxicity.
Topics: Abietanes; Antiviral Agents; Diterpenes; Diterpenes, Kaurane; Euphorbia; Phorbols; Phytochemicals
PubMed: 35944737
DOI: 10.1016/j.jep.2022.115574 -
Biochemistry and Cell Biology =... Dec 2023GPRC5A is the first member of a new class of orphan receptors coupled to G proteins, which also includes GPRC5B, GPRC5C, and GPRC5D. Since its cloning and identification... (Review)
Review
GPRC5A is the first member of a new class of orphan receptors coupled to G proteins, which also includes GPRC5B, GPRC5C, and GPRC5D. Since its cloning and identification in the 1990s, substantial progress has been made in understanding the possible functions of this receptor. has been implicated in a variety of cellular events, such as cytoskeleton reorganization, cell proliferation, cell cycle regulation, migration, and survival. It appears to be a central player in different pathological processes, including tumorigenesis, inflammation, immune response, and tissue damage. The levels of expression differ depending on the type of cancer, with increased expression in colon, pancreas, and prostate cancers; decreased expression in lung cancer; and varied results in breast cancer. In this review, we discuss the early discovery of as a phorbol ester-induced gene and later as a retinoic acid-induced gene, its regulation, and its participation in important canonical pathways related to numerous types of tumors and inflammatory processes. represents a potential new target for cancer, inflammation, and immunity therapies.
Topics: Male; Humans; Receptors, Retinoic Acid; Phorbol Esters; Receptors, G-Protein-Coupled; Lung Neoplasms; Inflammation; Tretinoin
PubMed: 37467514
DOI: 10.1139/bcb-2022-0352 -
Seminars in Cancer Biology Feb 2018Protein kinase C (PKC) has historically been considered an oncoprotein. This stems in large part from the discovery in the early 1980s that PKC is directly activated by... (Review)
Review
Protein kinase C (PKC) has historically been considered an oncoprotein. This stems in large part from the discovery in the early 1980s that PKC is directly activated by tumor-promoting phorbol esters. Yet three decades of clinical trials using PKC inhibitors in cancer therapies not only failed, but in some cases worsened patient outcome. Why has targeting PKC in cancer eluded successful therapies? Recent studies looking at the disease for insight provide an explanation: cancer-associated mutations in PKC are generally loss-of-function (LOF), supporting an unexpected function as tumor suppressors. And, contrasting with LOF mutations in cancer, germline mutations that enhance the activity of some PKC isozymes are associated with degenerative diseases such as Alzheimer's disease. This review provides a background on the diverse mechanisms that ensure PKC is only active when, where, and for the appropriate duration needed and summarizes recent findings converging on a paradigm reversal: PKC family members generally function by suppressing, rather than promoting, survival signaling.
Topics: Enzyme Activation; Genes, Tumor Suppressor; Humans; Isoenzymes; Mutation; Neoplasms; Phorbol Esters; Protein Kinase C; Signal Transduction
PubMed: 28476658
DOI: 10.1016/j.semcancer.2017.04.017 -
International Journal of Molecular... Dec 2022Breast cancer (BC) is a common female malignancy, worldwide. BC death is predominantly caused by lung metastasis. According to previous studies, Dihydrotanshinone I...
Breast cancer (BC) is a common female malignancy, worldwide. BC death is predominantly caused by lung metastasis. According to previous studies, Dihydrotanshinone I (DHT), a bioactive compound in Bunge (), has inhibitory effects on numerous cancers. Here, we investigated the anti-metastatic effect of DHT on BC, where DHT more strongly inhibited the growth of BC cells (MDA-MB-231, 4T1, MCF-7, and SKBR-3) than breast epithelial cells (MCF-10a). Additionally, DHT repressed the wound healing, invasion, and migration activities of 4T1 cells. In the 4T1 spontaneous metastasis model, DHT (20 mg/kg) blocked metastasis progression and distribution in the lung tissue by 74.9%. DHT reversed the formation of neutrophil extracellular traps (NETs) induced by phorbol 12-myristate 13-acetate, as well as ameliorated NETs-induced metastasis. Furthermore, it inhibited Ly6GMpo neutrophils infiltration and H3Cit expression in the lung tissues. RNA sequencing, western blot, and bioinformatical analysis indicated that could modulate DHT acting on lung metastasis inhibition. The study demonstrated a novel suppression mechanism of DHT on NETs formation to inhibit BC metastasis.
Topics: Female; Humans; Extracellular Traps; Breast Neoplasms; Phenanthrenes; Lung Neoplasms; Tetradecanoylphorbol Acetate; Neutrophils
PubMed: 36499502
DOI: 10.3390/ijms232315180 -
Cells Mar 2022Nociceptin and the nociceptin receptor (NOP) have been described as targets for treatment of pain and inflammation, whereas toll-like receptors (TLRs) play key roles in...
Nociceptin and the nociceptin receptor (NOP) have been described as targets for treatment of pain and inflammation, whereas toll-like receptors (TLRs) play key roles in inflammation and impact opioid receptors and endogenous opioids expression. In this study, interactions between the nociceptin and TLR systems were investigated. Human THP-1 cells were cultured with or without phorbol myristate acetate (PMA 5 ng/mL), agonists specific for TLR2 (lipoteichoic acid, LTA 10 µg/mL), TLR4 (lipopolysaccharide, LPS 100 ng/mL), TLR7 (imiquimod, IMQ 10 µg/mL), TLR9 (oligonucleotide (ODN) 2216 1 µM), PMA+TLR agonists, or nociceptin (0.01−100 nM). Prepronociceptin (ppNOC), NOP, and TLR mRNAs were quantified by RT-qPCR. Proteins were measured using flow cytometry. PMA upregulated ppNOC mRNA, intracellular nociceptin, and cell membrane NOP proteins (all p < 0.05). LTA and LPS prevented PMA’s upregulating effects on ppNOC mRNA and nociceptin protein (both p < 0.05). IMQ and ODN 2216 attenuated PMA’s effects on ppNOC mRNA. PMA, LPS, IMQ, and ODN 2216 increased NOP protein levels (all p < 0.05). PMA+TLR agonists had no effects on NOP compared to PMA controls. Nociceptin dose-dependently suppressed TLR2, TLR4, TLR7, and TLR9 proteins (all p < 0.01). Antagonistic effects observed between the nociceptin and TLR systems suggest that the nociceptin system plays an anti-inflammatory role in monocytes under inflammatory conditions.
Topics: Humans; Inflammation; Lipopolysaccharides; Opioid Peptides; RNA, Messenger; Tetradecanoylphorbol Acetate; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptor 7; Toll-Like Receptor 9; Toll-Like Receptors; Nociceptin
PubMed: 35406649
DOI: 10.3390/cells11071085 -
International Journal of Molecular... Nov 2022Neutrophil extracellular traps (NETs) are found in patients with various diseases, including cardiovascular diseases. We previously reported that copper-oxidized...
Neutrophil extracellular traps (NETs) are found in patients with various diseases, including cardiovascular diseases. We previously reported that copper-oxidized low-density lipoprotein (oxLDL) promotes NET formation of neutrophils, and that the resulting NETs increase the inflammatory responses of endothelial cells. In this study, we investigated the effects of high-density lipoproteins (HDL) on NET formation. HL-60-derived neutrophils were treated with phorbol 12-myristate 13-acetate (PMA) and further incubated with oxLDL and various concentrations of HDL for 2 h. NET formation was evaluated by quantifying extracellular DNA and myeloperoxidase. We found that the addition of native HDL partially decreased NET formation of neutrophils induced by oxLDL. This effect of HDL was lost when HDL was oxidized. We showed that oxidized phosphatidylcholines and lysophosphatidylcholine, which are generated in oxLDL, promoted NET formation of PMA-primed neutrophils, and NET formation by these products was completely blocked by native HDL. Furthermore, we found that an electronegative subfraction of LDL, LDL(-), which is separated from human plasma and is thought to be an in vivo oxLDL, was capable of promoting NET formation. These results suggest that plasma lipoproteins and their oxidative modifications play multiple roles in promoting NET formation, and that HDL acts as a suppressor of this response.
Topics: Humans; Lipoproteins, HDL; Extracellular Traps; Phospholipids; Endothelial Cells; Lipoproteins, LDL; Tetradecanoylphorbol Acetate
PubMed: 36430470
DOI: 10.3390/ijms232213992 -
Natural Product Research Jun 2022Two new tigliane diterpenes, named eupneonoids A () and B (), together with four known analogues () were isolated from the whole plant of Bruyns. Their structures were...
Two new tigliane diterpenes, named eupneonoids A () and B (), together with four known analogues () were isolated from the whole plant of Bruyns. Their structures were deduced based on the detailed spectroscopic analysis. All the isolates displayed cytotoxic effects against A549 human tumor cell lines with IC values ranging from 1.318 to 7.042 μM.
Topics: Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Diterpenes; Euphorbia; Humans; Molecular Structure; Phorbols
PubMed: 33960223
DOI: 10.1080/14786419.2021.1924712 -
Molecular Carcinogenesis Jun 2017Few kinases have been studied as extensively as protein kinase C (PKC), particularly in the context of cancer. As major cellular targets for the phorbol ester tumor... (Review)
Review
Few kinases have been studied as extensively as protein kinase C (PKC), particularly in the context of cancer. As major cellular targets for the phorbol ester tumor promoters and diacylglycerol (DAG), a second messenger generated by stimulation of membrane receptors, PKC isozymes play major roles in the control of signaling pathways associated with proliferation, migration, invasion, tumorigenesis, and metastasis. However, despite decades of research, fundamental questions remain to be answered or are the subject of intense controversy. Primary among these unresolved issues are the role of PKC isozymes as either tumor promoter or tumor suppressor kinases and the incomplete understanding on isozyme-specific substrates and effectors. The involvement of PKC isozymes in cancer progression needs to be reassessed in the context of specific oncogenic and tumor suppressing alterations. In addition, there are still major hurdles in addressing isozyme-specific function due to the limited specificity of most pharmacological PKC modulators and the lack of validated predictive biomarkers for response, which impacts the translation of these agents to the clinic. In this review we focus on key controversial issues and upcoming challenges, with the expectation that understanding the intricacies of PKC function will help fulfill the yet unsuccessful promise of targeting PKCs for cancer therapeutics.
Topics: Animals; Antineoplastic Agents; Diglycerides; Disease Progression; Humans; Isoenzymes; Molecular Targeted Therapy; Neoplasms; Phorbol Esters; Protein Kinase C; Substrate Specificity
PubMed: 28112438
DOI: 10.1002/mc.22617 -
BMC Veterinary Research May 2022Sheep are an important livestock species worldwide and an essential large-animal model for animal husbandry and veterinary research. Understanding fundamental immune...
BACKGROUND
Sheep are an important livestock species worldwide and an essential large-animal model for animal husbandry and veterinary research. Understanding fundamental immune indicators, especially T-lymphocyte parameters, is necessary for research on sheep diseases and vaccines, to better understand the immune response to bacteria and viruses for reducing the use of antibiotics and improving the welfare of sheep. We randomly selected 36 sheep of similar ages to analyze cell-related immune indicators in peripheral blood mononuclear cells (PBMCs). The proportions of CD4 and CD8 T cells in PBMCs were detected by flow cytometry. We used Concanavalin A (Con A) and Phorbol-12-myristate-13-acetate (PMA)/Ionomycin to stimulate PBMCs, and measured the expression of IFN-γ, IL-4, and IL-17A using enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISpot). Simultaneously, PMA/Ionomycin/brefeldin A (BFA) was added to PBMCs, then the expression of IFN-γ, IL-4, and IL-17A was detected by flow cytometry after 4 h of culturing. In addition, we observed the proliferation of PBMCs stimulated with Con A for 3, 4, and 5 days.
RESULTS
The proportions of CD4 T lymphocytes (18.70 ± 4.21%) and CD8 T lymphocytes (8.70 ± 3.65%) were generally consistent among individuals, with a CD4/CD8 ratio of 2.40 ± 0.79. PBMCs produced high levels of IFN-γ, IL-4, and IL-17A after stimulation with PMA/Ionomycin and Con A. Furthermore, PMA/Ionomycin stimulation of PBMC yielded significantly higher cytokine levels than Con A stimulation. Flow cytometry showed that the level of IFN-γ (51.49 ± 11.54%) in CD8 T lymphocytes was significantly (p < 0.001) higher than that in CD4 T lymphocytes (14.29 ± 3.26%); IL-4 (16.13 ± 6.81%) in CD4 T lymphocytes was significantly (p < 0.001) higher than that in CD8 T lymphocytes (1.84 ± 1.33%), There was no difference in IL-17A between CD4 (2.83 ± 0.98%) and CD8 T lymphocytes (1.34 ± 0.67%). The proliferation of total lymphocytes, CD4 T lymphocytes, and CD8 T lymphocytes continued to increase between days 3 and 5; however, there were no significant differences in proliferation between the cell types during the stimulation period.
CONCLUSIONS
Evaluating primary sheep immune indicators, especially T lymphocytes, is significant for studying cellular immunity. This study provided valuable data and theoretical support for assessing the immune response of sheep to pathogens and improving sheep welfare.
Topics: Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cytokines; Flow Cytometry; Interleukin-17; Interleukin-4; Ionomycin; Leukocytes, Mononuclear; Lymphocyte Activation; Sheep; Tetradecanoylphorbol Acetate
PubMed: 35513847
DOI: 10.1186/s12917-022-03268-7 -
Fitoterapia Jan 2021As part of a study on the structure-activity relationships of the anticancer agent tigilanol tiglate (EBC-46, 2), the allylic oxidation of phorbol triacetate (1c) and of...
As part of a study on the structure-activity relationships of the anticancer agent tigilanol tiglate (EBC-46, 2), the allylic oxidation of phorbol triacetate (1c) and of the acetonide of its 3αH-dihydroderivative (5) was investigated. The aim was to introduce an oxygen function at C-5 en route to point-like analogues of 2, but functionalization of C-10 was instead observed. This was followed by oxidative fragmentation of ring B to the 9,10-secotigliane derivative 6 and oxidation of the endocyclic Δ double bond to the C-6/C-10 oxygen bridged 7-oxotigliane 7. Despite the over-functionalization of ring B, these observations suggest the possibility to modify positions overlooked in the oxidase phase of tigliane biosynthesis and explore novel areas of the phorbol chemical space.
Topics: Antineoplastic Agents; Molecular Structure; Oxidation-Reduction; Phorbol Esters; Structure-Activity Relationship
PubMed: 33309651
DOI: 10.1016/j.fitote.2020.104802