Ursolic Acids Research Articles

UHPLC-DAD/ESI-TOF-MS Phytochemical Characterization and Evaluation of the Impact of Eleutherococcus senticosus Fruit Intractum on Biochemical, Hepatological, and Blood Parameters in Balb/c Mice.

Eleutherococcus senticosus (Rupr. et Maxim.) Maxim. (ES) has gained popularity for its adaptogenic, immunostimulant, and anti-inflammatory properties. Because of overexploitation of the roots, the species is considered to be endangered and has been put on the Red List in some countries (e.g., the Republic of Korea). Therefore, the fruits of E. senticosus might be explored as a new sustainable source of compounds with adaptogenic activity. This study aimed to assess the chemical composition and the safety profile (hepatotoxicity, blood morphology, biochemical parameters of blood plasma) of E. senticosus fruit intractum in Balb/c mice after oral administration of 750 and 1500 mg/kg b.w. UHPLC analysis coupled with DAD and MS detectors was used to quantify the metabolites. For the first time, oleanolic and ursolic acids were quantified in the intractum (16.01 ± 1.3 and 2.21 ± 0.17 µg/g of oleanolic and ursolic acids, respectively). Regarding polyphenols, chlorogenic acid (0.92 mg/g of dried extract), caffeic acid (0.43 mg/g), dicaffeoylquinic acids (in total: 1.27 mg/g), and an unidentified caffeic acid ester (0.81 mg/g) were identified. The results in Balb/c mice revealed that the intractum does not cause significant variations in red blood cells parameters. In turn, a significant decrease in the total number of leukocytes was observed (5.8 × 103 µL), with a percentage increase in lymphocytes among the groups (80.2, 81.8, and 82.6). The ability of the intractum to decrease alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels may indicate its anti-inflammatory activity. Our observations justify that the fruits of E. senticosus are safe in the doses used and do not cause significant changes in the activity of the liver enzymes or in blood parameters.

An Update on Pentacyclic Triterpenoids Ursolic and Oleanolic Acids and Related Derivatives as Anticancer Candidates.

Cancer is a global health problem, with the incidence rate estimated to reach 40% of the population by 2030. Although there are currently several therapeutic methods, none of them guarantee complete healing. Plant-derived natural products show high therapeutic potential in the management of various types of cancer, with some of them already being used in current practice. Among different classes of phytocompounds, pentacyclic triterpenoids have been in the spotlight of research on this topic. Ursolic acid (UA) and its structural isomer, oleanolic acid (OA), represent compounds intensively studied and tested in vitro and in vivo for their anticancer and chemopreventive properties. Since natural compounds can rarely be used in practice as such due to their characteristic physico-chemical properties, to tackle this problem, their derivatization has been attempted, obtaining compounds with improved solubility, absorption, stability, effectiveness, and reduced toxicity. This review presents various UA and OA derivatives that have been synthesized and evaluated in recent studies for their anticancer potential. It can be observed that the most frequent structural transformations were carried out at the C-3, C-28, or both positions simultaneously. It has been demonstrated that conjugation with heterocycles or cinnamic acid, derivatization as hydrazide, or transforming OH groups into esters or amides increases anticancer efficacy.

Synthesis and comparative analysis of the cytotoxicity and mitochondrial effects of triphenylphosphonium and F16 maslinic and corosolic acid hybrid derivatives

The cytotoxic profile and antiproliferative and mitochondrial effects of triterpene acid conjugates with mitochondriotropic lipophilic triphenylphosphonium (TPP+) and F16 cations were evaluated. Maslinic and corosolic acids chosen as the investigation objects were synthesized from commercially available oleanolic and ursolic acids. Study of the cytotoxic activity of TPP+ and F16 triterpenoid derivatives against six tumor cell lines demonstrated a comparable synergistic effect in the anticancer activity, which was most pronounced in the case of MCF-7 mammary adenocarcinoma cells and Jurkat and THP-1 leukemia cells. The corosolic and maslinic acid hybrid derivatives caused changes in the progression of tumor cell cycle phases when present in much lower doses than their natural triterpene acid precursors. The treatment of tumor cell lines with the conjugates resulted in the cell cycle arrest in the G1 phase and increase in the cell population in the subG1 phase. The cationic derivatives of the acids were markedly superior to their precursors as inducers of hyperproduction of reactive oxygen species and more effectively decreased the mitochondrial potential in isolated rat liver mitochondria. We concluded that the observed cytotoxic effect of TPP+ and F16 triterpenoid conjugates is attributable to the ability of these compounds to initiate mitochondrial dysfunctions. Their cytotoxicity, antiproliferative action, and mitochondrial effects depend little on the type of cationic groups used.

Betulinic and ursolic acids from Nauclea latifolia roots mediate their antimalarial activities through docking with PfEMP-1 and PfPKG proteins

BackgroundChemotherapies target the PfEMP-1 and PfPKG proteins in Plasmodium falciparum, the parasite that causes malaria, in an effort to prevent the disease’s high fatality rate. This work identified the phytochemical components of Nauclea latifolia roots and docked the chemical compounds against target proteins, and examined the in vivo antiplasmodial effect of the roots on Plasmodium berghei-infected mice.MethodsStandard protocols were followed for the collection of the plant’s roots, cleaning, and drying of the roots, extraction and fraction preparation, assessment of the in vivo antiplasmodial activity, retrieval of the PfEMP-1 and PfPKG proteins, GCMS, ADME, and docking studies, chromatographic techniques were employed to separate the residual fraction’s components, and the Swis-ADME program made it possible to estimate the drug’s likeness and pharmacokinetic properties. The Auto Dock Vina 4.2 tool was utilized for molecular docking analysis.ResultsThe residual fraction showed the best therapeutic response when compared favorably to amodiaquine (80.5%) and artesunate (85.1%). It also considerably reduced the number of parasites, with the % growth inhibition of the parasite at 42.8% (D2) and 83.4% (D5). Following purification, 25 compounds were isolated and characterized with GCMS. Based on their low molecular weights, non-permeation of the blood–brain barrier, non-inhibition of metabolizing enzymes, and non-violation of Lipinski’s criteria, betulinic and ursolic acids were superior to chloroquine as the best phytochemicals. Hence, they are lead compounds.ConclusionIn addition to identifying the bioactive compounds, ADME, and docking data of the lead compounds as candidates for rational drug design processes as observed against Plasmodium falciparum target proteins (PfEMP-1 and PfPKG), which are implicated in the pathogenesis of malaria, the study has validated that the residual fraction of N. latifolia roots has the best antiplasmodial therapeutic index.

Betulinic acid ameliorates cast‐immobilized skeletal muscle atrophy but not denervation‐induced skeletal muscle atrophy

AbstractBackgroundTerpenoids have gained attention as therapeutic agents for skeletal muscle atrophy owing to their various physiological activities. In this study, we screened four terpenoids for their therapeutic potential against muscle atrophy in cultured cells and evaluated the effectiveness of betulinic acid in two disuse muscle atrophy models.MethodsC2C12 cells were used as the skeletal muscle model in cell culture experiments. Betulinic acid (100 mg/kg, twice daily) was administered to two different mouse models of muscle atrophy (established using the sciatic denervation and casting methods) for 7 days.ResultsIn myotube experiments, the mRNA expression of atrogin‐1 and myostatin was significantly suppressed by betulinic and ursolic acids (P < 0.05). In the differentiation phase of C2C12 myotubes, the mRNA expression levels of myoD and myogenin were significantly increased by betulinic acid (P < 0.05). In addition, apelin and irisin were also significantly increased by betulinic acid (P < 0.05 and 0.01, respectively). Consequently, betulinic acid was administered to the aforementioned muscle atrophy models. Betulinic acid did not inhibit the decrease in skeletal muscle weight observed in the denervation model. However, it significantly inhibited the decrease in tibialis anterior (TA) and extensor digitorum longus (EDL) weights and grip strength observed in the cast‐immobilized skeletal muscle atrophy model (TA: Cast + Veh vs. Cast + Bet = 42.6 ± 1.0 vs. 46.0 ± 0.8 mg, P < 0.01; EDL: Cast + Veh vs. Cast + Bet = 9.0 ± 0.4 vs. 11.3 ± 0.5 mg, P < 0.01; grip strength: Cast + Veh vs. Cast + Bet = 222 ± 4.8 vs. 245 ± 3.6 g, P < 0.05). In addition, betulinic acid administration partially inhibited the decrease in skeletal muscle cross‐sectional area.ConclusionsBetulinic acid alleviated muscle atrophy in the cast model of muscle atrophy and has therapeutic potential for the treatment of immobilized disuse skeletal muscle atrophy.

Psidium guajava: An Insight into Ethnomedicinal Uses, Phytochemistry, and Pharmacology.

Psidium guajava (guava) is widely distributed in tropical and subtropical regions and adapted to various environmental conditions. Guava is an important economic fruit widely used as food and folk medicine. It contains flavonoids, alkaloids, tannins, triterpenoids, reducing sugars, essential oils, carotenoids, polyphenols, etc. The presence of triterpenoid acids such as guavacoumaric, ursolic, jacoumaric, guajavanoic, guavenoic, and Asiatic acids helps to develop novel drugs against various diseases. It is used traditionally for medicinal purposes, mainly for antioxidant, antimicrobial, antispasmodic, antidiabetic, anticancer, antiallergy, anti-inflammatory, and hepato-protective properties. The systematic literature study aims to summarize its botanical description, phytochemicals, pharmacological activities, and clinical trials. This review focuses on the plant's chemical composition and scientific approaches to human welfare. A systematic literature search was done on Psidium guajava through previous literature and online databases such as Google Scholar, Pubmed, Science Direct, etc., to explain its ethnomedicinal uses, phytochemistry, and pharmacological applications. Previous literature studies of Psidium guajava suggest it can serve as antioxidant, antimicrobial, antispasmodic, antidiabetic, anticancer, anti-allergy, anti-inflammatory, and hepatoprotective effects. Successful clinical trials performed on the plant extracts against infantile rotaviral enteritis and infectious gastroenteritis showed future directions to work with the plant for clinical applications. In this review, an attempt is made to show all literature studied, especially in phytochemistry, pharmacology, clinical trials and uses as traditional folk medicine around the world. The leaves have been used by folklore over the years to treat various ailments such as skin ulcers, diarrhoea, vaginal irritation, cough, conjunctivitis, etc. Further studies are required to explore more therapeutic remedies and to develop new medicines for future perspectives.

Phenological Variations in the Content of Polyphenols and Triterpenoids in Epilobium angustifolium Herb Originating from Ukraine.

The composition of secondary metabolites undergoes significant changes in plants depending on the growth phase and the influence of environmental factors. Therefore, it is important to determine the harvesting time of plant material for the optimum secondary metabolite profile and therapeutic activity of the primary material. The shoots of Epilobium angustifolium are used as a healing tea due to the presence of polyphenolic compounds. The aim of this study was to assess the composition of phenolic compounds and triterpenoid saponins in E. angustifolium leaves and flowers and to estimate the dynamics of their content depending on the flowering phase. Qualitative and quantitative characterisation of polyphenols and triterpenoids in E. angustifolium samples from Ukraine of three flowering phases were performed using the high-performance liquid chromatography photo diode array (HPLC-PDA) method. During the present study, 13 polyphenolic compounds and seven triterpenoids were identified in the plant material. It was noted that the largest content and the best polyphenol profile was in late flowering. The most important polyphenolic compounds in the plant material were chlorogenic acid, hyperoside, isoquercitin, and oenothein B. The triterpenoid profile was at its maximum during mass flowering, with corosolic and ursolic acids being the dominant metabolites. The results of the analysis revealed that the quantity of many of the tested metabolites in the raw material of E. angustifolium is dependent on the plant organ and flowering phase. The largest content of most metabolites in the leaves was in late flowering. In the flowers, the quantity of the metabolites studied was more variable, but decreased during mass flowering and increased significantly again in late flowering. The results show that E. angustifolium raw material is a potential source of oenothein B and triterpenoids.

A Comprehensive Study on Chemical and Biological Investigation of Thymus Brachychilus Jalas: A Rich Source of Ursolic and Oleanolic Acids

The significance of Thymus species in the scientific community is growing steadily due to their extensive utilization in traditional medicine, food industry, and pharmaceutical sector, owing to their abundance in essential oil and phytochemical content, rendering them commercially significant species. The current work focuses on conducting a comprehensive analysis of the ethanol extract and essential oil derived from the root and aerial portions of Thymus brachychilus Jalas, an endemic species that has not been previously investigated. Additionally, a novel GC-MS (gas chromatography–mass spectrometry) technique was developed to quantify the levels of triterpenoids, which are frequently found in many plants, particularly those belonging to the Lamiaceae family. The approach was then used to assess the triterpenoid content of the species. While the phenolic content of the species was determined by LC-MS/MS (liquid chromatography–tandem mass spectrometry), the chemical composition of triterpenoid, essential oil and flavor (aroma) of the plant was determined by GC-MS. Eucalyptol was the primary ingredient in both the essential oil and the flavor, accounting for 11.05% and 12.35%, respectively. In the DPPH and ABTS radical scavenging techniques, the root ethanol extract exhibited the greatest antioxidant activity with IC50 values of 26.70 ± 0.23 and 19.16 ± 0.11 µg/mL, respectively. There was a high level of urease (59.54 ± 1.67% at 100 µg/mL) inhibitory activity observed in the root ethanol extract in enzyme inhibition assays, as well as angiotensin (94.80 ± 0.56%), elastase (40.19 ± 0.39%), and collagenase (48.26 ± 0.12%) inhibition in the aerial ethanol extract. Moreover, the MCF-7 cell line for breast cancer had a strong cytotoxic impact when exposed to the essential oil of the species (vitality%: 1.45 ± 0.01 at 200 µg/mL. The LC-MS/MS and GC-MS studies revealed that the roots had a significant concentration of rosmarinic acid (15,801 µg analyte/g extract), but the aerial portions had a substantial quantity of ursolic acid (152,374 µg analyte/g extract). The plant exhibits potential in the food, cosmetic, and pharmaceutical sectors on account of its elevated levels of rosmarinic and ursolic acid, superior antioxidant capacity, and angiotensin and urease inhibitory effect.

A telomere-to-telomere reference genome provides genetic insight into the pentacyclic triterpenoid biosynthesis in Chaenomeles speciosa.

Chaenomeles speciosa (2n = 34), a medicinal and edible plant in the Rosaceae, is commonly used in traditional Chinese medicine. To date, the lack of genomic sequence and genetic studies has impeded efforts to improve its medicinal value. Herein, we report the use of an integrative approach involving PacBio HiFi (third-generation) sequencing and Hi-C scaffolding to assemble a high-quality telomere-to-telomere genome of C. speciosa. The genome comprised 650.4Mb with a contig N50 of 35.5Mb. Of these, 632.3Mb were anchored to 17 pseudo-chromosomes, in which 12, 4, and 1 pseudo-chromosomes were represented by a single contig, two contigs, and four contigs, respectively. Eleven pseudo-chromosomes had telomere repeats at both ends, and four had telomere repeats at a single end. Repetitive sequences accounted for 49.5% of the genome, while a total of 45 515 protein-coding genes have been annotated. The genome size of C. speciosa was relatively similar to that of Malus domestica. Expanded or contracted gene families were identified and investigated for their association with different plant metabolisms or biological processes. In particular, functional annotation characterized gene families that were associated with the biosynthetic pathway of oleanolic and ursolic acids, two abundant pentacyclic triterpenoids in the fruits of C. speciosa. Taken together, this telomere-to-telomere and chromosome-level genome of C. speciosa not only provides a valuable resource to enhance understanding of the biosynthesis of medicinal compounds in tissues, but also promotes understanding of the evolution of the Rosaceae.

Miconia albicans (Melastomataceae) to treat Chikungunya viral infection: An effectual symptom-driven ethnomedicinal repurposing of an anti-inflammatory species?

Ethnopharmacological relevanceMiconia albicans (MA) is consumed all over the Brazilian territory as a remedy to treat rheumatoid arthritis and has been increasingly used to alleviate the deleterious symptoms caused by Chikungunya virus (CHIKV). Aim of the studyTo investigate the effect of MA leaf and stem hydroethanolic extracts (LE and SE, respectively), their fractions enriched in triterpene acids or polyphenols as well isolated constituents, on CHIKV hosted in Vero cells. Materials and methodsPolyphenol profiles of LE and SE were dereplicated by HPLC-DAD-ESI-MS/MS, aided by standards. Polyphenol-rich (LEx and SEx) and triterpenic acid-rich (LOH and SOH) fractions were obtained in Amberlite XAD-4 and alkalinized 95% ethanol (EtOH) extraction, respectively. TPC and TFC were assessed by colorimetric methods. Three representative flavonoids and two triterpenic acids were quantified by HPLC. CHIKV load suppression was evaluated in Vero cells by real-time qRT‒PCR at noncytotoxic concentrations. ResultsFifteen flavonoids were characterized in LE and SE. LEx presented isoquercitrin, quercitrin, rutin (0.49–1.51%) and quercetin. The TPC was 48 and 62 mg QE/g extract, and the TFC was 11.93 and 0.76 mg QE/g extract for LEx and SEx, respectively. LOH presented ursolic (15.3%) and oleanolic (8.0%) acids. A reduction (91–97%) in the CHIKV load was produced by the triterpene fraction, quercitrin and quercetin; the latter maintained the activity down to one twentieth of the tolerated concentration. ConclusionM. albicans contains flavonoids and triterpenic acids that are effective against CHIKV, which might justify its use to alleviate sequelae of CHIKV infection. However, further investigations on the species and its active constituents are needed.

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.

Conjugation of Triterpenic Acids of Ursane and Oleanane Types with Mitochondria-Targeting Cation F16 Synergistically Enhanced Their Cytotoxicity against Tumor Cells.

The present work shows the cytotoxic effects of novel conjugates of ursolic, oleanolic, maslinic, and corosolic acids with the penetrating cation F16 on cancer cells (lung adenocarcinoma A549 and H1299, breast cancer cell lines MCF-7 and BT474) and non-tumor human fibroblasts. It has been established that the conjugates have a significantly enhanced toxicity against tumor-derived cells compared to native acids and also demonstrate selectivity to some cancer cells. The toxic effect of the conjugates is shown to be due to ROS hyperproduction in cells, induced by the effect on mitochondria. The conjugates caused dysfunction of isolated rat liver mitochondria and, in particular, a decrease in the efficiency of oxidative phosphorylation, a decrease in the membrane potential, and also an overproduction of ROS by organelles. The paper discusses how the membranotropic- and mitochondria-targeted effects of the conjugates may be related to their toxic effects.

Determination of Pentacyclic Triterpenoids in Plant Biomass by Porous Graphitic Carbon Liquid Chromatography-Tandem Mass Spectrometry.

Pentacyclic triterpenoids (PCTs), which possess a number of bioactive properties, are considered one of the most important classes of secondary plant metabolites. Their chromatographic determination in plant biomass is complicated by the need to separate a large number of structurally similar compounds belonging to several classes that differ greatly in polarity (monools, diols, and triterpenic acids). This study proposes a rapid, sensitive, and low-cost method for the simultaneous quantification of ten PCTs (3β-taraxerol, lupeol, β-amyrin, α-amyrin, betulin, erythrodiol, uvaol, betulinic, oleanolic, and ursolic acids) by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) using porous graphitic carbon (Hypercarb) as a stationary phase capable of hydrophobic retention and specific interactions with analytes. Revealing the effects of the mobile phase composition, pH, ionic strength, and column temperature on retention and selection of chromatographic conditions on this basis allowed for the effective separation of all target analytes within 8 min in gradient elution mode and attaining limits of detection in the range of 4-104 µg L-1. The developed method was fully validated and successfully tested in the determination of PCTs in common haircap (Polytrichum commune) and prairie sphagnum (Sphagnum palustre) mosses, and fireweed (Chamaenerion angustifolium) stems and leaves.

OeBAS and CYP716C67 catalyze the biosynthesis of health-beneficial triterpenoids in olive (Olea europaea) fruits.

The bioactive properties of olive (Olea europaea) fruits and olive oil are largely attributed to terpenoid compounds, including diverse triterpenoids such as oleanolic, maslinic and ursolic acids, erythrodiol, and uvaol. They have applications in the agri-food, cosmetics, and pharmaceutical industries. Some key steps involved in the biosynthesis of these compounds are still unknown. Genome mining, biochemical analysis, and trait association studies have been used to identify major gene candidates controlling triterpenoid content of olive fruits. Here, we identify and functionally characterize an oxidosqualene cyclase (OeBAS) required for the production of the major triterpene scaffold β-amyrin, the precursor of erythrodiol, oleanolic and maslinic acids, and a cytochrome P450 (CYP716C67) that mediates 2α oxidation of the oleanane- and ursane-type triterpene scaffolds to produce maslinic and corosolic acids, respectively. To confirm the enzymatic functions of the entire pathway, we have reconstituted the olive biosynthetic pathway for oleanane- and ursane-type triterpenoids in the heterologous host, Nicotiana benthamiana. Finally, we have identified genetic markers associated with oleanolic and maslinic acid fruit content on the chromosomes carrying the OeBAS and CYP716C67 genes. Our results shed light on the biosynthesis of olive triterpenoids and provide new gene targets for germplasm screening and breeding for high triterpenoid content.

Triterpenoids in Jujube: A Review of Composition, Content Diversity, Pharmacological Effects, Synthetic Pathway, and Variation during Domestication.

Chinese jujube (Ziziphus jujuba Mill.) and its wild ancestor, sour jujube (Z. acidojujuba C.Y. Cheng & M.J. Liu), is a Ziziphus genus in the Rhamnaceae family. ZJ and ZA are rich in a variety of active ingredients, with triterpenoids being a unique active ingredient, which are present in the fruit, leaves, branches, and roots. More than 120 triterpenoids have been identified in ZJ and ZA, and have various biological activities. For example, betulinic and ursolic acids have anticancer, antioxidant, antibacterial and antiviral activities. ceanothic, alphitolic, and zizyberanalic acids possess anti-inflammatory activities. The MVA pathway is a synthetic pathway for triterpenoids in ZJ and ZA, and 23 genes of the MVA pathway are known to regulate triterpene synthesis in ZJ and ZA. In order to better understand the basic situation of triterpenoids in ZJ and ZA, this paper reviews the types, content dynamic changes, activities, pharmacokinetics, triterpenoid synthesis pathways, and the effects of domestication on triterpenoids in ZJ and ZA, and provides some ideas for the future research of triterpenoids in ZJ and ZA. In addition, there are many types of ZJ and ZA triterpenoids, and most of the studies on their activities are on lupane- and ursane-type triterpenes, while the activities of the ceanothane-type and saponin are less studied and need additional research.

Exploiting the Integrated Valorization of Eucalyptus globulus Leaves: Chemical Composition and Biological Potential of the Lipophilic Fraction before and after Hydrodistillation.

E. globulus leaves have been mainly exploited for essential oil recovery or for energy generation in industrial pulp mills, neglecting the abundance of valuable families of extractives, namely, triterpenic acids, that might open new ways for the integrated valorization of this biomass. Therefore, this study highlights the lipophilic characterization of E. globulus leaves before and after hydrodistillation, aiming at the integrated valorization of both essential oils and triterpenic acids. The lipophilic composition of E. globulus leaves after hydrodistillation is reported for the first time. Extracts were obtained by dichloromethane Soxhlet extraction and analyzed by gas chromatography-mass spectrometry. In addition, their cytotoxicity on different cell lines representative of the innate immune system, skin, liver, and intestine were evaluated. Triterpenic acids, such as betulonic, oleanolic, betulinic and ursolic acids, were found to be the main components of these lipophilic extracts, ranging from 30.63-37.14 g kg-1 of dry weight (dw), and representing 87.7-89.0% w/w of the total content of the identified compounds. In particular, ursolic acid was the major constituent of all extracts, representing 46.8-50.7% w/w of the total content of the identified compounds. Other constituents, such as fatty acids, long-chain aliphatic alcohols and β-sitosterol were also found in smaller amounts in the studied extracts. This study also demonstrates that the hydrodistillation process does not affect the recovery of compounds of greatest interest, namely, triterpenic acids. Therefore, the results establish that this biomass residue can be considered as a promising source of value-added bioactive compounds, opening new strategies for upgrading pulp industry residues within an integrated biorefinery context.

Potential Role of Oleanolic and Ursolic Acids from Food and Plant Materials as Natural Ingredients for the Cosmetic Industry: A Review

Cosmeceuticals have emerged as health and beauty aid products that integrate active ingredients from natural sources. Phytochemicals have prevailed in this market as an effective alternative toward different skin conditions. This is mainly due to the increasing demand for natural products that overcome the side effects of conventional treatments. Alopecia, acne, and skin aging are prevalent skin-related conditions worldwide. These conditions are characterized by high levels of inflammatory biomarkers and oxidative stress conditions. Oleanolic and ursolic acids are two biologically active pentacyclic triterpenoid isomeric compounds. They have shown strong potential for the prevention and treatment of diverse skin-related conditions through their effective antioxidant and anti-inflammatory capacity. This review presents the latest available information on the biological potential of oleanolic and ursolic acids, highlighting their cosmeceutical potential. In the pursuit of a better understanding of their potential as natural ingredients of dermatological relevance, graphical analysis is provided to propose the molecular mechanisms involved in the effects of each skin-related condition.

Effect directed analysis of bioactive compounds in leaf extracts from two Salvia species by High-performance thin-layer chromatography

Extracts of two Salvia species, Salvia apiana (white sage) and Salvia officinalis (common sage) were screened for phytoconstituents with the ability to act as antidiabetic, cognitive enhancing, or antimicrobial agents, by hyphenation of high-performance thin-layer chromatography with enzymatic and microbial effect directed assays. Two bioactive zones with α-amylase inhibition (zone 1 and zone 2), 3 zones for acetylcholinesterase inhibition (zones 3, 4 and 5), and two zones for antimicrobial activity (zones 4 and 5) were detected. The compounds from the five bioactive zones were initially identified by coelution with standards and comparing the RF values of standards to the bioautograms. Identity was confirmed with ATR-FTIR spectra of the isolated compounds from the bioactive zones. A significantly higher α-amylase and acetylcholinesterase inhibition of S. apiana leaf extract was associated with a higher flavonoid and diterpenoid content. Fermented S. officinalis extract exhibited a significantly higher ability to inhibit α-amylase compared to other non-fermented extracts from this species, due to increased extraction of flavonoids. The ATR-FTIR spectra of 2 zones with α-amylase inhibition, indicated that flavonoids and phenolic acids were responsible for α-amylase inhibition. Multiple zones of acetylcholinesterase inhibition were related to the presence of phenolic abietane diterpenoids and triterpenoid acids. The presence of abietane diterpenoids and triterpenoid acids was also found responsible for the mild antimicrobial activity. Flash chromatography was used to isolate sufficient amounts of bioactive compounds for further characterisation via NMR and MS spectroscopy. Five compounds were assigned to the zones where bioactivity was observed: cirsimaritin (zone 1), a caffeic acid polymer (zone 2), 16-hydroxyrosmanol (zone 3), 16-hydroxycarnosic acid (zone 4), oleanolic and ursolic acids (zone 5).

Fractionation and Characterization of Triterpenoids from Vaccinium vitis-idaea L. Cuticular Waxes and Their Potential as Anticancer Agents.

Fruit and leaf cuticular waxes are valuable source materials for the isolation of triterpenoids that can be applied as natural antioxidants and anticancer agents. The present study aimed at the semi-preparative fractionation of triterpenoids from cuticular wax extracts of Vaccinium vitis-idaea L. (lingonberry) leaves and fruits and the evaluation of their cytotoxic potential. Qualitative and quantitative characterization of obtained extracts and triterpenoid fractions was performed using HPLC-PDA method, followed by complementary analysis by GC-MS. For each fraction, cytotoxic activities towards the human colon adenocarcinoma cell line (HT-29), malignant melanoma cell line (IGR39), clear renal carcinoma cell line (CaKi-1), and normal endothelial cells (EC) were determined using MTT assay. Furthermore, the effect of the most promising samples on cancer spheroid growth and viability was examined. This study allowed us to confirm that particular triterpenoid mixtures from lingonberry waxes may possess stronger cytotoxic activities than crude unpurified extracts. Fractions containing triterpenoid acids plus fernenol, complexes of oleanolic:ursolic acids, and erythrodiol:uvaol were found to be the most potent therapeutic candidates in the management of cancer diseases. The specificity of cuticular wax extracts of lingonberry leaves and fruits, leading to different purity and anticancer potential of obtained counterpart fractions, was also enclosed. These findings contribute to the profitable utilization of lingonberry cuticular waxes and provide considerable insights into the anticancer effects of particular triterpenoids and pharmacological interactions.

Optimization of Cyclodextrin-Assisted Extraction of Phenolics from Helichrysum italicum for Preparation of Extracts with Anti-Elastase and Anti-Collagenase Properties

Helichrysum italicum is a plant traditionally used for skin-related disorders that is becoming an increasingly popular ingredient in cosmetic products. In this work, a "green" ultrasound-assisted extraction method for H. italicum phenolics was developed using skin-friendly cyclodextrins (CDs). Extraction conditions needed for the greatest yield of target compounds (total phenolics, phenolic acids, and flavonoids) were calculated. The composition of the extracts was determined using LC-MS and spectrophotometric methods. Among the tested CDs, 2-hydroxylpropyl-beta-CD (HP-β-CD) was the best suited for extraction of target phenolics and used to prepare two optimized extracts, OPT 1 (the extract with the highest phenolic acid content) and OPT 2 (the extract with the highest total phenol and flavonoid content). The extracts were prepared at 80 °C, using 0.089 g of plant material/g solvent (0.6 mmol of HP-β-CD), with or without addition of 1.95% (w/w) lactic acid. The main metabolite in both extracts was 3,5-O-dicaffeoylquinic acid. It was found that the addition of lactic acid greatly contributes to the extraction of arzanol, a well-known anti-inflammatory agent. IC50 values of the anti-elastase (22.360 ± 0.125 μL extract/mL and 20.067 ± 0.975 for OPT-1 and OPT-2, respectively) and anti-collagenase (12.035 ± 1.029 μL extract/mL and 14.392 ± 0.705 μL extract/mL for OPT-1 and OPT-2, respectively) activities of the extracts surpassed those of the applied positive controls, namely ursolic and gallic acids. This activity deems the prepared extracts promising ingredients for natural cosmetics, appropriate for direct use in cosmetic products, removing the need for the evaporation of conventional solvents.