Pomolic Acid Research Articles

Alendronate Functionalized Bone-Targeting Pomolic Acid Liposomes Restore Bone Homeostasis for Osteoporosis Treatment.

Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem. Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis. However, its poor solubility and lack of targeting severely limits its further application. A novel bone-targeting nanomedicine (PA@TLipo) has been developed to reconstruct the osteoporotic microenvironment by encapsulating pomolic acid in alendronate-functionalized liposomes. Through a series of operations such as synthesis, purification, encapsulation, and labeling, the PA@TLipo have been prepared. Moreover, the cytotoxicity, bone targeting and anti-osteoporosis effect was verified by cell and animal experiments. In the aspect of targeting, the PA@TLipo can effectively aggregate on the bone tissue to reduce bone loss, and in terms of toxicity, PA@TLipo could increase the bone target ability in comparison to nontargeted liposome, thereby mitigating systemic cytotoxicity. Moreover, PA@TLipo inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice. In this study, a novel therapeutic agent was designed and constructed to treat osteoporosis, consisting of a liposome material as the drug pocket, PA as the anti-osteoporosis drug, and ALN as the bone-targeting molecule. And our study is the first to employ a bone-targeted delivery system to deliver PA for OVX-induced bone loss, providing an innovative solution for treating osteoporosis.

Exploring the binding interactions of NOP receptor with designed natural phytochemical-neuropeptide conjugates: an in silico and SPR study

The Nociceptin/orphanin FQ peptide (NOP) receptor is considered a member of the opioid receptor subfamily of G-protein coupled receptors (GPCRs) which has been shown to be present in many parts of the central nervous system (CNS). It plays biologically diverse roles in pain modulation, immune response and in neurodegenerative diseases. In this work, phytochemical conjugates of two known neuropeptides, melanocyte inhibition factor (MiF-1) and mammalian amidated neuropeptide NPFF with pain modulating ability were developed. The binding interactions of those conjugates with NOP receptor was examined as an approach to develop novel natural compounds that can modulate NOP receptor activity. The selected phytochemicals are well-known for their antioxidant abilities and are derived either from natural alkaloids (betanin), polyphenols (gallic acid and sinapic acid) or terpenes (pomolic acid). Each of the phytochemicals selected are antioxidants which may play a role in mitigating diseases. Three conjugates of betanin were designed with each peptide by conjugating each of the three carboxylic acid groups of betanin with the peptides, while all others were mono-conjugates. Our results indicated that the betanin conjugates with both peptides showed strong binding interactions while the pomolate-peptide conjugates showed moderate binding. In general, NPFF and its conjugates showed stronger binding with the receptor. Docking and molecular dynamics studies revealed that binding interactions occurred at the binding pocket encompassing the transmembrane helices TM1, TM3 and TM7 in most cases, with the ligands binding deep within the hydrophobic core. The binding interactions were further confirmed experimentally through SPR analysis, which also showed higher binding with the betanin conjugates. MMGBSA studies indicated that the binding energies of MiF-1 conjugates were higher compared to neat MiF-1. However, in the case of NPFF, while the betanin conjugates showed enhancement, in some cases the binding energies were found to be slightly reduced compared to neat NPFF. Overall our studies reveal that such natural phytochemical derivatives that can bind to the NOP receptor when conjugated to the mammalian amidated neuropeptide NPFF and the short sequence of melanocyte inhibiting factor MiF-1 may be potentially developed for further laboratory studies for potential pharmaceutical applications.

Secondary metabolites from Sarcosperma kontumense

Six urs-ketone triterpenes (1 - 6) and two flavonoids (7, 8) from the leaves of Sarcosperma kontumense Gagnep. ex Aubrév., were isolated. Their chemical structures were elucidated as 2α,3α,19α,23-tetrahydroxy-13,27-cyclours-11-en-28-oic acid (1), rotundic acid (2), euscaphic acid (3), ursolic acid (4), pomolic acid (5), jacoumaric acid (6), (+)-catechin (7), and (-)-epi-catechin (8), by spectroscopic analyses including ESI-MS, 1D and 2D NMR spectra and comparison with those reported in the literatures. In which, compounds 1, 2, 4, 6, and 8 were firstly isolated from the genus Sarcosperma.

Antibacterial and Antioxidant Superoxide Anion Radical Inhibitors from Myrmecodia pendans: An In silico Study

Background: Background: Ant-nest (Myrmecodia pendans) is an epiphytic plant that can prevent several diseases, including bacterial infections. Diarrhea is caused by Escherichia coli bacteria, while infections in the oral cavity can be caused by Enterococcus faecalis bacteria. Antibacterial activity is also influenced by conditions of Reactive Oxygen Species (ROS). Antioxidants are needed to inhibit the formation of excess ROS in the body. Superoxide anion radicals are included in the generation of ROS, which is produced by several enzymes, such as nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase or commonly known as Nox and xanthine oxidase (XO). Objective: This study aimed to determine the potential of M. pendans as an antibacterial in vitro and in silico correlation in the formation of superoxide anion radicals. Methods: The compounds were obtained by column chromatography method, followed by a spectroscopic examination. In vitro test using the disc diffusion method and in silico test using AutoDock 4.2 program were conducted with positive control fosfomycin and allopurinol, tethered to MurA, Nox, and XO enzymes, and visualized using the Discovery Studio 2020. Results: Compound 1 (oleanolic acid) and compound 2 (pomolic acid) demonstrated antibacterial activity against E. coli but no activity against E. faecalis. Compound 3 (3-hydroxy-eupan-20,24-dien-26-oic acid) demonstrated no activity against these two bacteria. Based on the in silico results, compound 3 had the best binding energy affinity for all MurA, Nox, and XO enzymes of -6.89, -9.35, and -9.75 Kcal/mol, respectively. Similarly, compounds 1 and 2 had good binding energies for Nox protein of -9.29 Kcal/mol and -6.54 Kcal/mol and XO of -7.66 and -4.7 Kcal/mol, respectively. Conclusion: In vitro results against E. coli and E. faecalis bacteria showed inhibition by compounds 1 and 2 but not by compound 3. Meanwhile, in in silico analysis, all the compounds showed potential as an inhibitor of superoxide anion radicals generated by enzymes Nox and XO.

Pomolic acid and its glucopyranose ester promote apoptosis through autophagy in HT-29 colon cancer cells.

Colon cancer remains a leading cause of death globally. Pomolic acid (PA) can be separated from the ethyl acetate fraction of achyrocline satureioides. To determine the effects of PA and its glucopyranose ester, pomolic acid-28-O-β-D-glucopyranosyl ester (PAO), on colon cancer HT-29 cells. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay was used to measure cell viability. Apoptosis was detected via hoechst 33342 staining. PI single staining was identified by flow cytometry to determine the cycle and scratch assay was used to observe the migration of HT-29 cells. The levels of mRNA and proteins were evaluated by q polymerase chain reaction and western blotting, respectively. PA and PAO considerably inhibited the growth of the HT-29 cell line in a time and dose-dependent manner. After the administration of PA and PAO for 24 and 48 h, cell apoptosis was significantly promoted and HT-29 cells were arrested in the G0/G1 stage. The Bax/Bcl2 ratio was also increased, which activated cysteinyl aspartate specific proteinase 3, leading to apoptosis; it also increased the expression of light chain 3 II/I and Beclin1, which activated autophagy and caused cell death. This in turn increased the expression of p62 to promote cell apoptosis, inhibiting the levels of signal transducer and activator of transcription 3 (STAT3) and p-STAT3, suppressing the level of Bcl2, and promoting cell. Both PA and PAO provide novel therapeutic strategies for treating colorectal cancer.

Enzyme immobilized on magnetic fluorescent bifunctional nanoparticles for α-glucosidase inhibitors virtual screening from Agrimonia pilosa Ledeb extracts accompanied with molecular modeling

Agrimonia pilosa Ledeb (APL) is a significant source of inhibitors for α-glucosidase, which is an essential target enzyme for the treatment of type 2 diabetes, cancer and acquired immune deficiency syndrome. Ligand fishing is a suitable approach for the highly selective screening of bioactive substances in complex mixtures. Yet it is unable to conduct biomedical imaging screening, which is crucial for real-time identification. In this case, a bioanalytical platform combining magnetic fluorescent ligand fishing and in-situ imaging technique was established for the screening and identification of α-glucosidase inhibitors (AGIs) from APL crude extract, utilizing α-glucosidase coated CuInS2/ZnS-Fe3O4@SiO2 (AG-CIZSFS) nanocomposites as extracting material and fluorescent tracer. The AG-CIZSFS nanocomposites prepared through solvothermal and crosslinking methods displayed fast magnetic separation, excellent fluorescence performance and high enzyme activity. The tolerance of immobilized enzyme to temperature and pH was stronger than that of free enzyme. Prior to proof-of-concept with APL crude extract, a number essential parameters (glutaraldehyde concentration, immobilized time, enzyme amount, reaction solution pH, incubation temperature, incubation time, percentage of methanol in eluen, elution times and eluent volume) were optimized using an artificial test mixture. The fished ligands were identified by UPLC-MS/MS and their biological activities were preliminarily evaluated by real-time cellular morphological imaging of human colon carcinoma (HCT-116) cells based on confocal laser scanning microscope (CLSM). Their α-glucosidase inhibitory activities were further verified and studied by classical pNPG method and molecular docking. The isolated compounds exhibited significant α-glucosidase inhibitory activities with a IC50 value of 11.57 µg·mL−1. Six potential AGIs including tribuloside, ivorengenin A, tormentic acid, 1β, 2β, 3β, 19α-Tetra hydroxyurs-12-en-28-oic acid, corosolic acid and pomolic acid were ultimately screened out and identified from APL crude extracts. The proposed approach, which combined highly specific screening with in-situ visual imaging, provided a powerful platform for discovering bioactive components from multi-component and multi-target traditional Chinese medicine (TCM).

Clethra fimbriata hexanic extract triggers alteration in the energy metabolism in epimastigotes of Trypanosoma cruzi.

Chagas disease (ChD), caused by Trypanosoma cruzi, is endemic in American countries and an estimated 8 million people worldwide are chronically infected. Currently, only two drugs are available for therapeutic use against T. cruzi and their use is controversial due to several disadvantages associated with side effects and low compliance with treatment. Therefore, there is a need to search for new tripanocidal agents. Natural products have been considered a potential innovative source of effective and selective agents for drug development to treat T. cruzi infection. Recently, our research group showed that hexanic extract from Clethra fimbriata (CFHEX) exhibits anti-parasitic activity against all stages of T. cruzi parasite, being apoptosis the main cell death mechanism in both epimastigotes and trypomastigotes stages. With the aim of deepening the understanding of the mechanisms of death induced by CFHEX, the metabolic alterations elicited after treatment using a multiplatform metabolomics analysis (RP/HILIC-LC-QTOF-MS and GC-QTOF-MS) were performed. A total of 154 altered compounds were found significant in the treated parasites corresponding to amino acids (Arginine, threonine, cysteine, methionine, glycine, valine, proline, isoleucine, alanine, leucine, glutamic acid, and serine), fatty acids (stearic acid), glycerophospholipids (phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine), sulfur compounds (trypanothione) and carboxylic acids (pyruvate and phosphoenolpyruvate). The most affected metabolic pathways were mainly related to energy metabolism, which was found to be decrease during the evaluated treatment time. Further, exogenous compounds of the triterpene type (betulinic, ursolic and pomolic acid) previously described in C. fimbriata were found inside the treated parasites. Our findings suggest that triterpene-type compounds may contribute to the activity of CFHEX by altering essential processes in the parasite.

Rapid Chemical Profiling of Filipendula ulmaria Using CPC Fractionation, 2-D Mapping of 13C NMR Data, and High-Resolution LC-MS.

Filipendula ulmaria, commonly known as meadowsweet, is a wild herbaceous flowering plant that is widely distributed in Europe. A range of salicylic acid derivatives and flavonol glycosides have been previously associated with the antirheumatic and diuretic properties of F. ulmaria. In the present work, a hydroalcoholic extract from F. ulmaria aerial parts was extensively profiled using an efficient NMR-based dereplication strategy. The approach involves the fractionation of the crude extract by centrifugal partition chromatography (CPC), 13C NMR analysis of the fractions, 2D-cluster mapping of the entire NMR dataset, and, finally, structure elucidation using a natural metabolite database, validated by 2D NMR data interpretation and liquid chromatography coupled with mass spectrometry. The chemodiversity of the aerial parts was extensive, with 28 compounds unambiguously identified, spanning various biosynthetic classes. The F. ulmaria extract and CPC fractions were screened for their potential to enhance skin epidermal barrier function and skin renewal properties using in vitro assays performed on Normal Human Epidermal Keratinocytes. Fractions containing quercetin, kaempferol glycosides, ursolic acid, pomolic acid, naringenin, β-sitosterol, and Tellimagrandins I and II were found to upregulate genes related to skin barrier function, epidermal renewal, and stress responses. This research is significant as it could provide a natural solution for improving hydration and skin renewal properties.

Triterpenoids and Indole Alkaloids from the Aerial Parts of Asystasia gangetica (L.) T. Anderson

Asystasia gangetica (L.) T. Anderson is an edible vegetable, cultivated in Vietnam. This plant was reported to contain a diverse chemical composition including megastimans, flavonoids, iridoids, and phenylpropanoid glycosides. It also exhibited many interesting biological activities such as antibacterial, antifungal, antihypertensive, anti-asthmatic, analgesic, anti-inflammatory, tyrosinase inhibitory, antioxidant, and antidiabetic effects. However, so far, the studies on this species in Vietnam are relatively few. In this study, six compounds including lutein (1), verbascoside (2), indole-3-carboxylic acid (3), 3α,24-dihydroxy-olean-12-en-28-oic acid (4), ursolic acid (5), and pomolic acid (6) were isolated from the ethyl acetate fraction of the aerial parts of A. gangetica. Their structures were identified based on the NMR and MS spectroscopic data and comparison with those in the literature. Four compounds (3-6) have been isolated from this plant for the first time.

Identification, quantitative determination and isolation of pomolic acid from lavender (Lavandula angustifolia Mill.) wastes

Lavender essential oil production wastes have been investigated as a highly available source of pentacyclic triterpenic acids. Ultrasound assisted extraction was addressed as a simple and scalable procedure for efficient production of enriched extracts from dry plant material with good yields. Flowers and stalks have been processed separately. Analytical studies have been performed basing on both HPLC and qNMR methods. The qNMR analysis proved to be a much more convenient alternative to HPLC and its application resulted in identification, isolation and quantitative determination of substantial amounts of pomolic acid in the obtained extracts, along with widely explored ursolic and oleanolic acids. The ultrasound assisted extraction of lavender flowers with 96% ethanol resulted in a 3.3% yield of triterpenic acids, with a substantial share of pomolic acid that constitutes 1% of the plant material dry weight. Selective extraction of flowers with ethylacetate resulted in an enriched product containing 67.8% of triterpenic acids, including 16.2% of pomolic acid. Quantification of pomolic acid is reported for the first time in this vegetal source. These results demonstrate the relevant potential of lavender wastes as a sustainable raw material for the production of pomolic acid - a highly valued compound of increased nutraceutical and pharmaceutical interest.

Assessment of Antioxidant and Polyphenol Profile of Chrysobalanus icaco from Southern Nigeria

Due to the distinguished medicinal value of Chrysobalanus icaco, it was of great interest to conduct phytochemical and antioxidant investigations on it. In this study, the polyphenol profile and antioxidant activity of C. icaco methanol crude extract and fractions were investigated. The crude extract of C. icaco was subjected to fractionation using methanol, n-hexane, ethyl acetate, and n-butanol as solvents. 2, 2-diphenyl-1picryl-hydrazyl (DPPH), 2,2’-azino-bis-(3- ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing power (FRAP), ascorbate oxidase, total phenolic content, total flavonoids and polyphenol profile was determined using standard methods. A significant increase was observed in the DPPH radical scavenging activity, total flavonoids, total phenol, FRAP, ABTS, TAC and ascorbate oxidase of the crude extract when compared to methanol, ethyl acetate, n-hexane, n-butanol, and aqueous fractions. Polyphenols such as kaempferol, chlorogenic acid, catechin, quercetin, galic acid, pomolic acid, rutin, epicatechin, stigmasterol, sitosterol and caffeic acid were found in the different fractions. The total polyphenols content of different fractions of C icaco extract were as follows; methanol fraction > n-hexane fraction > ethyl acetate fraction > n-butanol fraction > aqueous fraction. The findings revealed that C icaco kernel could be used as a potent source of molecules with positive health attributes.

Characterization and antimicrobial evaluation of anthraquinones and triterpenes from Rubia cordifolia

Chemical investigation of roots of the plant, Rubia cordifolia Linn, led to the isolation of an undescribed anthraquinone, cordifoquinone R, determined as 1,2-dihydroxy-6-methoxyanthracene-9,10-dione (6) based on the 1D and 2D NMR analyses and HRESIMS. Ten other known compounds viz.1,4-dihydroxy-2-methoxyanthracene-9,10-dione (1), rubiadin (2), xanthopurpurin (3), 1-methoxy-3-hydroxy-2-carbomethoxy-9,10-anthraquinone (4), alizarin (5), β-sitosterol glucoside (7), scopoletin (8), oleanolic acid, (9), pomolic acid (10), queretaroic acid (11) were also isolated. Out of these compounds, 4, 10, and 11 are first reported from this plant species. Compounds 2, 3, 6, 7, and 10 showed activity in the range of 16-32 µg/ml against S. aureus ATCC 29213.

Identification and Analysis of Metabolites That Contribute to the Formation of Distinctive Flavour Components of Laoxianghuang.

In addition to volatile compounds, metabolites also have a great effect on the flavour of food. Fresh finger citron cannot be eaten directly because of its spicy and bitter taste, so it is made into a preserved fruit product known as Laoxianghuang (LXH). To investigate the metabolites that have an effect on the flavour of LXH, untargeted metabolomics was performed using an ultrahigh-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS), and the metabolites of the Laoxianghuang samples from different locations in the Chaoshan area were compared and analysed. A total of 756 metabolites were identified and distinct differences were revealed among the different Laoxianghuang samples. A total of 33 differential metabolites with the most significant changes were screened through further multivariate analytical steps, and each group of samples had unique metabolites. For instance, pomolic acid had the highest content in the JG sample, while L-glycyl-L-isoleucine was rich in the QS sample. Moreover, flavonoid metabolites made the greatest contribution to the unique flavour of Laoxianghuang. The metabolic pathways involved are the biosynthetic pathways of flavonoids, isoflavonoids, flavones, and flavonols. This study can provide some creative information for distinguishing the quality differences of Laoxianghuang from the perspective of metabolites and offer preliminary theoretical support to characterise the formation of flavour substances in Laoxianghuang.

Pomolic acid: A short review on its chemistry, plant sources, pharmacological properties, and patents

Clerodendrum serratum: A clinical approachMukesh Kr. Singh, Gaurav Khare, Shiv Kr. Iyer, Gotmi Sharwan, D. K. Tripathi

Chemical constituents and cytotoxic activity of Ocimum gratissimum L.

• The leaves of Ocimum gratissimum L. was subjected to identification of its chemical constituents. • The in vitro cytotoxic activity of compounds against lung adenocarcinoma (A549), breast carcinoma (MCF-7), acute monocytic leukemia (THP-1), murine macrophages Raw 264.7 cancer cell lines and the normal fibroblast A7R5 cell line were studied. • THP-1 was the most sensitive to compounds 1-6 . • Compound 4 and paclitaxel have similar IC 50 value against THP-1 cells. Malignancies constitute a global health concern and chemotherapy remains the main mode of treatment. The present study was designed to evaluate the cytotoxicity of metabolites isolated from Ocimum gratissimum L. The phytochemical investigation of the leaves of O. gratissimum L. (Lamiaceae) led to the isolation and characterization of eight compounds. Structures of isolated compounds were elucidated using 1D and 2D NMR, as well as MS. The purified compounds, were identified as five triterpenes ( 1-5 ), one flavonoid ( 6 ) and two steroidal compounds ( 7-8 ). The cytotoxicity effects of purified compounds were assessed in vitro by the WST-1 assay on three cancer cell lines including lung adenocarcinoma (A549), breast carcinoma (MCF-7), acute monocytic leukemia (THP-1), murine macrophages (Raw 264.7) and the normal fibroblast (A7R5) cells. Compound 4 had an IC 50 value of 3.21±0.4 µM similar to that of the reference drug, paclitaxel against THP-1 cells. The THP-1 cell lines were the most sensitive to compounds 1-6 . All the compounds showed low cytotoxicity against the normal cell line A7R5 as compared to cancer cell lines. The constituents of Ocimum gratissimum L. and especially pomolic acid ( 4 ) is a potent cytotoxic compound that deserves more investigations toward developing novel antiproliferative drugs against acute monocytic leukemia (THP-1).

Sarcokontums A and B, Two New 13,27-Cyclo-Pentacyclic Triterpenes from the Stems and Leaves of Sarcosperma kontumense Gagnep. ex Aubrév

Two new 13,27-cyclo pentacyclic triterpenes (1 and 2), together with ten pentacyclic triterpenoids (3-12), were characterized from the stems and leaves of Sarcosperma kontumense Gagnep. ex Aubrév. Their chemical structures were elucidated by spectroscopic analyses including HRESIMS, and 1D and 2D NMR spectra as 2 α,3 β,19 α,23-tetrahydroxy-13,27-cyclours-11-en-28-oic acid (1), 2 α,3 β,19 α,23-tetrahydroxy-13,27-cycloolean-11-en-28-oic acid (2), 2 α,3 α,19 α,23-tetrahydroxy-13,27-cyclours-11-en-28-oic acid (3), corosolic acid (4), pomolic acid (5), masilinic acid (6), 1 β,2 α,3α,19 α,23-pentahydroxyurs-11-en-28-oic acid (7), rotundic acid (8), euscaphic acid (9), jacoumaric acid (10), 3- O- trans-coumaroyltormetic acid (11), and 3- O- cis-coumaroyltormetic acid (12). Compounds 3, 4, 6-8, and 10-12 were isolated from the genus Sarcosperma for the first time.

Simultaneous Determination and Pharmacokinetics Study of Three Triterpenes from Sanguisorba officinalis L. in Rats by UHPLC–MS/MS

A selective and rapid ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was established and validated for the determination of ziyuglycoside I, 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, and pomolic acid in rats after the oral administration of ziyuglycoside I, 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, pomolic acid, and Sanguisorba officinalis L. extract. The separation was carried out on an ACQUITY UPLC®HSS T3 column (2.1 mm × 100 mm, 1.8 μm), using methanol and 5 mmol/L ammonium acetate water as the mobile phase. The three compounds were quantified using the multiple reaction monitoring mode with the electrospray ion source in both the positive and negative mode. Liquid-liquid extraction was applied to the plasma sample preparation. Bifendate was selected as the internal standard. The intra-day and inter-day precision and the accuracy of the method were all within receivable ranges. The lower limit of quantification of ziyuglycoside I, 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, and pomolic acid were 6.50, 5.75, and 2.63 ng/mL, respectively. The extraction recoveries of analytes in rat plasma ranged from 83 to 94%. The three components could be rapidly absorbed into the blood (Tmax, 1.4–1.6 h) both in the single-administration group or S. officinalis extract group, but the first peak of PA occurred at 0.5 h and the second peak at 4–5 h in the S. officinalis extract. Three compounds were eliminated relatively slowly (t1/2, 7.3–11 h). The research was to establish a rapid, sensible, and sensitive UHPLC–MS/MS method using the multi-ion mode for multi-channel simultaneous mensuration pharmacokinetics parameters of three compounds in rats after oral administration of S. officinalis extract. This study found, for the first time, differences in the pharmacokinetic parameters of the three compounds in the monomer compounds and S. officinalis extract administration, which preliminarily revealed the transformation and metabolism of the three compounds in vivo.

Pomolic acid inhibits proliferation of human lung carcinoma cells via induction of apoptosis and suppression of cell migration and invasion

Purpose: To investigate the anti-proliferative effect of pomolic acid on lung cancer cells (A549), and theunderlying mechanism.Methods: The viability of pomolic acid-treated A549 cells was determined by MTT and colony formation assays. Cell colony formation was monitored with acridine orange/ethidium bromide (AO/EB) staining. Protein expressions of Bax and Bcl-2 were assayed by western blotting.Results: Pomolic acid suppressed the growth of A549 cells, with an half-maximal inhibitory concentration of (IC50) of 10 μM (p < 0.05). However, the IC50 of pomolic acid for normal BEAS-2B cells was 80 μM. Pomolic acid also decreased colony formation of A549 cells. At 20 μM, the percentage of A549 colonies decreased to 14 % of control. The dose-dependent cytotoxicity of pomolic acid against A549 cells was mediated via induction of apoptosis and oxidative stress. Pomolic acid treatment enhanced the expression of Bax and decreased the expression of Bcl-2 in A549 cells. Moreover, pomolic acid inhibited the migration and invasion in A549 cells in a dose-dependent manner (p < 0.05).Conclusion: These results indicate the potent anticancer effect of pomolic acid against human lung cancer cells. Thus, pomolic acid has promising potential as a lead molecule for the development of chemotherapy.

Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part II).

Triterpenic acids are a widespread class of phytocompounds which have been found to possess valuable therapeutic properties such as anticancer, anti-inflammatory, hepatoprotective, cardioprotective, antidiabetic, neuroprotective, lipolytic, antiviral, and antiparasitic effects. They are a subclass of triterpenes bearing a characteristic lipophilic structure that imprints unfavorable in vivo properties which subsequently limit their applications. The early investigation of the mechanism of action (MOA) of a drug candidate can provide valuable information regarding the possible side effects and drug interactions that may occur after administration. The current paper aimed to summarize the most recent (last 5 years) studies regarding the MOA of betulinic acid, boswellic acid, glycyrrhetinic acid, madecassic acid, moronic acid, and pomolic acid in order to provide scientists with updated and accessible material on the topic that could contribute to the development of future studies; the paper stands as the sequel of our previously published paper regarding the MOA of triterpenic acids with therapeutic value. The recent literature published on the topic has highlighted the role of triterpenic acids in several signaling pathways including PI3/AKT/mTOR, TNF-alpha/NF-kappa B, JNK-p38, HIF-α/AMPK, and Grb2/Sos/Ras/MAPK, which trigger their various biological activities.

New Terpenoids from Potentilla freyniana Bornm. and Their Cytotoxic Activities.

Two new A-ring contracted triterpenoids, madengaisu A and madengaisu B, and one undescribed ent-kaurane diterpenoid, madengaisu C, along with 20 known compounds were isolated from the roots of Potentilla freyniana Bornm. The structures were elucidated using extensive spectroscopic techniques, including 1D and 2D-NMR, HR-ESI-MS, ECD spectra, IR, and UV analysis. Moreover, all isolated constituents were evaluated for their anti-proliferative activity against RA-FLS cells and cytotoxic activities against the human cancer cell lines Hep-G2, HCT-116, BGC-823, and MCF-7. Ursolic acid and pomolic acid displayed moderate inhibitory activity in RA-FLS cells with IC50 values of 24.63 ± 1.96 and 25.12 ± 1.97 μM, respectively. Hyptadienic acid and 2α,3β-dihydroxyolean-12-en-28-oic acid 28-O-β-d-glucopyranoside exhibited good cytotoxicity against Hep-G2 cells with IC50 values of 25.16 ± 2.55 and 17.66 ± 1.82 μM, respectively. In addition, 2α,3β-dihydroxyolean-13(18)-en-28-oic acid and alphitolic acid were observed to inhibit HCT-116 cells (13.25 ± 1.65 and 21.62 ± 0.33 μM, respectively), while madengaisu B and 2α,3β-dihydroxyolean-13(18)-en-28-oic acid showed cytotoxic activities against BGC-823 cells with IC50 values of 24.76 ± 0.94 and 26.83 ± 2.52 μM, respectively, which demonstrated that triterpenes from P. freyniana may serve as therapeutic agents for RA and cancer treatment.