Extensive targeted metabolomics analysis reveals the identification of major metabolites, antioxidants, and disease-resistant active pharmaceutical components in Camellia tuberculata (Camellia L.) seeds.

Sect. tuberculata plant belongs to the Camellia genus and is named for the "tuberculiform protuberance on the surface of the ovary and fruit". It is a species of great ornamental value and potential medicinal value. However, little has been reported on the metabolites of C. tuberculata seeds. Therefore, this study was conducted to investigate the metabolites of C. tuberculata seeds based on UPLC/ESI-Q TRAP-MS/MS with extensively targeted metabolomics. A total of 1611 metabolites were identified, including 107 alkaloids, 276 amino acids and derivatives, 283 flavonoids, 86 lignans and coumarins, 181 lipids, 68 nucleotides and derivatives, 101 organic acids, 190 phenolic acids, 10 quinones, 4 steroids, 17 tannins, 111 terpenoids, and 177 other metabolites. We compared the different metabolites in seeds between HKH, ZM, ZY, and LY. The 1311 identified different metabolites were classified into three categories. Sixty-three overlapping significant different metabolites were found, of which lignans and coumarins accounted for the largest proportion. The differentially accumulated metabolites were enriched in different metabolic pathways between HKH vs. LY, HKH vs. ZM, HKH vs. ZY, LY vs. ZY, ZM vs. LY and ZM vs. ZY, with the most abundant metabolic pathways being 4, 2, 4, 7, 7 and 5, respectively (p < 0.05). Moreover, among the top 20 metabolites in each subgroup comparison in terms of difference multiplicity 7, 8 and 13. ZM and ZY had the highest phenolic acid content. Ninety-six disease-resistant metabolites and 48 major traditional Chinese medicine agents were identified based on seven diseases. The results of this study will not only lead to a more comprehensive and in-depth understanding of the metabolic properties of C. tuberculata seeds, but also provide a scientific basis for the excavation and further development of its medicinal value.

The Antioxidant, Anti-Inflammatory and Moisturizing Effects of Camellia oleifera Oil and Its Potential Applications.

Camellia oleifera oil (CO oil) extracted from C. oleifera seeds has a 2300-year consumption history in China. However, there is relatively little research regarding its non-edible uses. This study determined the physicochemical properties of CO oil extracted via direct pressing, identified its main components using GC-MS, and evaluated its antioxidant, moisturizing, and anti-inflammatory activities. The results revealed that CO oil's acid, peroxide, iodine, and saponification values were 1.06 ± 0.031 mg/g, 0.24 ± 0.01 g/100 g, 65.14 ± 8.22 g/100 g, and 180.41 ± 5.60 mg/g, respectively. CO oil's tocopherol, polyphenol, and squalene contents were 82.21 ± 9.07 mg/kg, 181.37 ± 3.76 mg/kg, and 53.39 ± 6.58 mg/kg, respectively; its unsaturated fatty acid (UFA) content was 87.44%, and its saturated fatty acid (SFA) content was 12.56%. CO oil also demonstrated excellent moisture retention properties, anti-inflammatory effects, and certain free radical scavenging. A highly stable CO oil emulsion with competent microbiological detection was developed using formulation optimization. Using CO oil in the emulsion significantly improved the formulation's antioxidant and moisturizing properties compared with those of the emulsion formulation that did not include CO oil. The prepared emulsion was not cytotoxic to cells and could reduce cells' NO content; therefore, it may have potential nutritional value in medicine and cosmetics.

In-field and non-destructive determination of comprehensive maturity index and maturity stages of Camellia oleifera fruits using a portable hyperspectral imager.

To efficiently detect the maturity stages of Camellia oleifera fruits, this study proposed a non-invasive method based on hyperspectral imaging technology. First, a portable hyperspectral imager was used for the in-field image acquisition of Camellia oleifera fruits at three maturity stages, and ten quality indexes were measured as reference standards. Then, factor analysis was performed to obtain the comprehensive maturity index (CMI) by analyzing the change trends and correlations of different indexes. To reduce the high dimensionality of spectral data, the successive projection algorithm (SPA) was employed to select effective feature wavelengths. The prediction models for CMI, including partial least squares regression (PLSR), support vector regression (SVR), extreme learning machine (ELM), and convolutional neural network regression (CNNR), were constructed based on full spectra and feature wavelengths; for CNNR, only the raw spectra were used as input. The SPA-CNNR model exhibited more promising performance (RP = 0.839, RMSEP = 0.261, and RPD = 1.849). Furthermore, PLS-DA models for maturity discrimination of Camellia oleifera fruits were developed using full wavelength, characteristic wavelengths and their fusion CMI, respectively. The PLS-DA model using the fused dataset achieved the highest maturity classification accuracy, with the best simplified model achieving 88.6 % accuracy in prediction set. This study indicated that a portable hyperspectral imager can be used for in-field determination of the internal quality and maturity stages of Camellia oleifera fruits. It provides strong support for non-destructive quality inspection and timely harvesting of Camellia oleifera fruits in the field.

Multifaceted analysis of the effects of roasting conditions on the flavor of fragrant Camellia oleifera Abel. seed oil.

Fragrant Camellia oleifera Abel. seed oil (FCSO), produced by a roasting process, is popular for its characteristic aroma. This study investigated the effects of various roasting temperatures (90℃, 120℃, 150℃, 180℃) and durations (20 min, 40 min, 60 min) on the flavor of FCSO by physicochemical properties, hazardous substances, sensory evaluation, and flavor analyses. The results showed that FCSO roasted at 120℃/20 min had a reasonable fatty acid composition with a lower acid value (0.16 mg/g), peroxide value (0.13 g/100 g), p-anisidine value (2.27), dibutyl phthalate content (0.04 mg/kg), and higher 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity (224.51 µmol TE/kg) than other samples. A multivariate analysis of FCSO flavor revealed that the 120℃/20 min group had a higher grassy flavor score (5.3 score) from nonanoic acid and a lower off-flavor score (2.2 score) from 2-methylbutyric acid. The principal component analysis showed that 120℃/20 min could guarantee the best flavor and quality of FCSO. Therefore, this information can guide the preparation of FCSO.

The effect of extraction methods on the components and quality of Camellia oleifera oil: Focusing on the flavor and lipidomics.

The objective of this study was to systematically elucidate the effects of conventional (Cold Pressing, CP; Hot Pressing, HP; Soxhlet Extraction; SE) and novel methods (Microwave-Assisted Extraction, MAE) on the physicochemical properties, bio-active substances, flavor and lipidomics of Camellia oleifera oil (COO). The cold-pressed COO contained the highest contents of squalene (176.38 mg/kg), α-tocopherol (330.52 mg/kg), polyphenols (68.33 mg/kg) and phytosterols (2782.55 mg/kg). Oleic acid was observed as the predominant fatty acid with the content of approximately 80%. HS-GC-IMS identified 47 volatile compounds, including 11 aldehydes, 11 ketones, 11 alcohols, 2 acids, 8 esters, 2 pyrazines, 1 furan, and 1 thiophene. A total of 5 lipid classes and 30 lipid subclasses of 339 lipids were identifed, among which TGs and DGs were observed as the major lipids. In summary, both cold-pressed and microwave-assisted technologies provided high-quality COO with high content of bio-active substances and diglycerides/triglycerides.

Advances in Separation, Biological Properties, and Structure-Activity Relationship of Triterpenoids Derived from Camellia oleifera Abel.

Extensive research has been conducted on Camellia oleifera Abel., a cultivar predominantly distributed in China, to investigate its phytochemical composition, owning to its potential as an edible oil crop. Pentacyclic triterpene saponins, as essential active constituents, play a significant role in contributing to the pharmacological effects of this cultivar. The saponins derived from C. oleifera (CoS) offer a diverse array of bioactivity benefits, including antineoplastic/bactericidal/inflammatory properties, cardiovascular protection, neuroprotection, as well as hypoglycemic and hypolipidemic effects. This review presents a comprehensive analysis of the isolation and pharmacological properties of CoS. Specially, we attempt to reveal the antitumor structure-activity relationship (SAR) of CoS-derived triterpenoids. The active substitution sites of CoS, namely, C-3, C-15, C-16, C-21, C-22, C-23, and C-28 pentacyclic triterpenoids, make it a unique and highly valuable substance with significant medicinal and culinary applications. As such, CoS can play a critical role in transforming people's lives, providing unique medicinal benefits, and contributing to the advancement of both medicine and cuisine.

Phenolic and flavonoid compounds from the fruit shell of Camellia oleifera.

A new phenolic compound oleiphenol (1), and a new dihydrochalcone oleifechalcone (2) along with seven known compounds (3-9) were isolated from the fruit shell of Camellia oleifera Abel. The planar structures of compounds 1 and 2 were determined on the basis of extensive spectroscopic analyses (IR, UV, NMR, and HR-ESI-MS) and comparison with literature data. The absolute configurations of the new structures were determined by ECD calculations and chemical methods. In addition, compounds 1-9 underwent a series of pharmacological activity tests, including cytotoxic, anti-inflammatory, anti-RSV and antioxidant activities.

A novel strategy by combining foam fractionation with high-speed countercurrent chromatography for the rapid and efficient isolation of antioxidants and cytostatics from Camellia oleifera cake.

Camellia oleifera cake is a by-product, which is rich in functional chemical components. However, it is typically used as animal feed with no commercial value. The purpose of this study was to isolate and identify compounds from Camellia oleifera cake using a combination of foam fractionation and high-speed countercurrent chromatography (HSCCC) and to investigate their biological activities. Foam fractionation with enhanced drainage through a hollow regular decahedron (HRD) was first established for simultaneously enriching flavonoid glycosides and saponins for further separation of target compounds. Under suitable operating conditions, the introduction of HRD resulted in a threefold increase in enrichment ratio with no negative effect on recovery. A novel elution-extrusion countercurrent chromatography (EECCC) coupled with the consecutive injection mode was established for the successful simultaneous isolation of flavonoid glycosides and saponins. As a result, 38.7 mg of kaemferol-3-O-[2-O-D-glucopyranosyl-6-O-α-L-rhamnopyranosyl]-ß-D-glucopyranoside (purity of 98.17%, FI), 70.8 mg of kaemferol-3-O-[2-O-ß-D-xylopyranosyl-6-O-α-L-rhamnopyranosyl]-ß-D-glucopyranoside (purity of 97.52%, FII), and 560 mg of an oleanane-type saponin (purity of 92.32%, FIII) were separated from the sample (900 mg). The present study clearly showed that FI and II were natural antioxidants (IC50 < 35 µg/mL) without hemolytic effect. FIII displayed the effect of inhibiting Hela cell proliferation (IC50 < 30 µg/mL). Further erythrocyte experiments showed that this correlated with the extremely strong hemolytic effect of FIII. Overall, this study offers a potential strategy for efficient and green isolation of natural products, and is beneficial to further expanding the application of by-products (Camellia oleifera cake) in food, cosmetics, and pharmacy.

Enrichment process, structural prediction, isolation, in vitro cytotoxic and anti-inflammatory effects of triterpenoid saponins in Camellia japonica L. leaves water extract through UPLC-Q-TOF based mass spectrometry similarity networking.

Camellia japonica L. is rich in bioactive compounds, but its health-enhancing potential is often overshadowed by its ornamental value. Notably, triterpenoid saponins are prominent due to their surfactant properties. MolNetEnhancer revealed 537 compounds in C. japonica leaves water extract, classified into 32 categories, including 38 triterpenoid saponins. To enrich triterpenoid saponins, the process of D101 resin chromatography was employed. Molecular networking analysis based on UPLC-Q-TOF and quantitative analysis based on HPLC revealed saponins concentrated in fractions 3 and 4 (68.3% transfer). MS2LDA and NAP predicted structures for 38 triterpenoid saponins, revealing nearly half of them are potential new compounds. Comprehensive chromatographic and spectroscopic methods were used for purification and structural illustration of triterpenoid saponins, yielding 13, including 7 new compounds. Statistical analysis and in vitro assays revealed the cytotoxic and anti-inflammatory activities of these triterpenoid saponins played a crucial role in the anticancer effects.

Foam and fluid properties of purified saponins and non-purified water extracts from Camellia oleifera cake (by-product).

The physicochemical and foam properties of non-purified water extracts (WE) and purified tea saponins (TS) from Camellia oleifera cake (byproduct) were compared. WE showed different fluid properties at equal saponin concentrations (1.0 wt%) compared to TS. Particularly, it exhibited limited micelle size (average 434.1 nm), effective viscosity (0.15 Pa·s), and surface tension (43.9 mN/m) independently of pH. Moreover, the foam properties of WE were comparable to TS and better than sodium caseinate, especially foam stability. WE foam was more stable than TS foam under pH (3-7) and heating (40-80 °C). In the presence of NaCl, sucrose, and ethanol (5-20 wt%), WE and TS were effective and had similar foam behavior. Low concentrations of sucrose (<10 wt%)/ethanol (<20 wt%) significantly increased the foam capacity, while ethanol over 30 wt% was unfavorable. WE/TS foam contributes significantly to the desired physicochemical and sensory attributes (taste, texture, and appearance) of foods.

Triterpenes and Pheophorbides from Camellia ptilosperma and Their Cytotoxicity, Photocytotoxicity, and Photodynamic Antibacterial Activity.

Phytochemical investigation of the leaves of Camellia ptilosperma S. Y. Liang et Q. D. Chen led to the isolation of ten undescribed compounds, including six new triterpenes (1-6) and four new pheophorbide-related compounds (7-10). Meanwhile, the cytotoxic activity of the six triterpenes against six cancer cell lines was evaluated by MTT assay. Compound 2 showed potent cytotoxicity toward HepG2 cells with an IC50 value of 2.57 µM. Compounds 4 and 5 exhibited cytotoxicity against MDA-MB231 cells, with IC50 values of 11.31 and 5.52 µM, respectively. Additionally, the cytotoxicity of four new pheophorbides against these cancer cells was evaluated both in the presence and absence of light treatment. Compound 7 exhibited exceptional photocytotoxicity against Hela, MCF-7, and A549 cells, with IC50 values of 0.43 µM, 0.28 µM, and 0.92 µM, respectively. Compound 10 demonstrated significant photodynamic cytotoxic activity against BEL-7402 and HepG2 cells with IC50 values of 0.77 µM and 0.33 µM, respectively. The photodynamic antibacterial activity of 7-10 was also tested for S. aureus, E. coli, K. pneumoniae, and P. aeruginosa under direct illumination. Compounds 8 and 10 exhibited sensitivity to E. coli and demonstrated a photodynamic antibacterial effect, with a MIC value of 0.625 µM.

Green extraction of polysaccharides from Camellia oleifera fruit shell using tailor-made deep eutectic solvents.

Camellia oleifera fruit shells are often discarded as byproducts in the C. oleifera industry. There is a general interest in isolating high-value natural products to valorize those fruit shells with green, rapid, and effective extraction methods. This study employed 43 combinations of deep eutectic solvents (DESs) to extract polysaccharides from C. oleifera fruit shells. Two choline chloride-based DESs and a ternary DES with propionic acid and 1,3-butanediol as hydrogen bond donors exhibited relatively high extraction efficiency. The polysaccharide yield reached 15.03 ± 0.35 % under optimized extraction time (55 min), extraction temperature (70 °C), and DES water content (33.33 %). The physicochemical composition and preliminary structure of obtained polysaccharides were characterized. Additionally, DESs-extracted polysaccharides exhibited higher in vitro antioxidant activities and hypoglycemic effects compared to water-extracted polysaccharides. These findings suggested that the optimized DES-assisted extraction method could be a potential approach for polysaccharides extraction from C. oleifera.

Antioxidant potential evaluation of polysaccharides from Camellia oleifera Abel in vitro and in vivo.

The extraction process, structural characterization and free radical scavenging ability of polysaccharides from Camellia oleifera have already been widely studied. However, the antioxidant activities are still lack of systematic experiments. In this study, we used Hep G2 cells and Caenorhabditis elegans to evaluate the antioxidant potential of polysaccharides that from C. oleifera flowers (P-CF), leaves (P-CL), seed cakes (P-CC) and fruit shells (P-CS). The results showed all these polysaccharides could protect cells from oxidative damage induced by t-BHP. The highest cell viabilities were 66.46 ± 1.36 % (P-CF), 55.2 ± 2.93 % (P-CL), 54.49 ± 1.29 % (P-CC) and 61.45 ± 1.67 % (P-CS), respectively. Studies have shown that four polysaccharides may protect cells from apoptosis by reducing ROS levels and maintaining MMP balance. Moreover, P-CF, P-CL, P-CC and P-CS increased the survival rate of C. elegans under thermal stress, which reduced the production of ROS by 56.1 ± 0.67 %, 59.37 ± 1.79 %, 16.63 ± 2.51 % and 27.55 ± 2.62 %, respectively. P-CF and P-CL showed stronger protective effects on C. elegans by increasing the nuclear entry rate of DAF-16 and stimulating the expression of SOD-3. Our study suggested that C. oleifera polysaccharides have the potential to develop into a natural supplement agent.

Highly efficient isolation and purification of high-purity tea saponins from industrial camellia oil production by porous polymeric adsorbents.

BACKGROUND: Recovery of high-purity tea saponin (TS), a promising non-ionic surfactant with well-documented properties, is one of the major challenges to broadening its industrial applications. In this study, an innovative and sustainable strategy for the highly-efficient purification of TS was developed by using well-designed highly-porous polymeric adsorbents. RESULTS: The prepared Pp-A with controllable macropores (~96 nm) and appropriate surface hydrophobic properties was found more favorable for achieving high adsorption efficiency towards TS/TS-micelles. Kinetic results showed the adsorption follows the pseudo-second-order model (R2 = 0.9800), and the Langmuir model is more qualified to explicate the adsorption isotherms with Qe-TS ~ 675 mg g-1 . Thermodynamic studies revealed the monolayer adsorption of TS was an endothermic process that was conducted spontaneously. Interestingly, ethanol-driven desorption (90% v/v ethanol) of TS was rapidly (< 30 min) complete due to the possible ethanol-mediated disassembling of TS-micelles. A possible mechanism that involves the interactions between the adsorbents and TS/TS-micelles, the formation and disassembling of TS-micelles was proposed to account for the highly efficient purification of TS. Afterwards, Pp-A-based adsorption method was developed to purify TS directly from industrial camellia oil production. Through selective adsorption, pre-washing, and ethanol-driven desorption, the applied Pp-A enabled the direct isolation of high-purity TS (~96%) with a recovery ratio > 90%. Notably, Pp-A exhibited excellent operational stability and is of high potential for long-term industrial application. CONCLUSION: Results ensured the practical feasibility of the prepared porous adsorbents in purifying TS, and the proposed methodology is a promising industrial-scale purification strategy. © 2023 Society of Chemical Industry.

Metabolomic profiles and health-promoting functions of Camellia drupifera mature-seeds were revealed relate to their geographical origins using comparative metabolomic analysis and network pharmacology approach.

To insight into the chemical components and their health-promoting function of Camellia drupifera mature-seeds (CMS) in Hainan and Liangguang, UPLC-MS/MS- and HS-SPME/GC-MS-based metabolomic analyses and network pharmacology approaches were combined preformed to Camellia drupifera mature-seeds samples (CMSSs). Totally, 1057 metabolites were identified, of which 76 and 99 metabolites were annotated as key active ingredients in Traditional Chinese Medicines and the active pharmaceutical ingredients for seven human disease-resistance, respectively. Comparative analysis revealed different metabolomic profiles of CMSSs from Hainan and Liangguang. KEGG annotation and enrichment analysis showed secondary metabolic pathways, especially "flavone and flavonol biosynthesis", were played important roles. Finally, 22 metabolites that only detected in CMSSs from Hainan or Liangguang were explored as potential indicators to separate CMS from Hainan out of Liangguang. Our findings enhanced the understanding of chemical compositions of CMS and provided valuable information for the healthy development of oil-tea Camellia industry in Hainan.

Ursane-Type Triterpenes with a Phenylpropanoid Unit from Camellia ptilosperma and Evaluation of Their Cytotoxic Activities.

Six new ursane-type triterpenes with a phenylpropanoid unit and five known oleanane-type triterpenes were isolated from the leaves of Camellia ptilosperma. The undescribed compounds were identified by analysis of 1D and 2D NMR and HRESIMS spectroscopic data as ptilospermanols A-F. The cytotoxicity of new compounds against six human cancer cell lines and three mouse tumor cell lines was evaluated by MTT assay.

Insight into the medium-long-medium structured lipids made from Camellia oil: Composition-structure relationship.

Medium-long-medium (MLM) structured lipid (SL) as a new SL is a potential functional ingredient in food and nutraceutical products, but its composition-structure-physicochemical properties relationship has not been revealed in food industry. MLM type of medium-long chain triacylglycerol (MLCT) was synthesized from Camellia oil by combi-lipase; its physicochemical properties and composition-structure relationship were investigated in this research. The higher MLCT (67.24% ± 0.09) and MLM (52.71% ± 0.53) productivities were achieved after parameter optimization. The physicochemical characterization of SLs exhibited mild thermal property, intermediate Fourier transform infrared spectroscopy absorption intensity, and better crystal morphology. Joint characterizations identified that MLM and long-medium-long type SL were rich in 1,3-dioctanoyl-2-linoleoyl glyceride (CaLCa), 1,3-dioctanoyl-2-oleoyl glyceride (CaOCa), 1,3-dilinoleoyl-2-octanoyl glyceride (LCaL), and 1,3-dilinoleoyl-2-decanoyl glyceride (LCL) components, respectively. This is ascribed to the higher proportion of caprylic and linoleic acid in 1,3-specific enzyme. The 3D structural analysis further demonstrated that the CaLCa, CaOCa, LCaL, and LCL molecules had lower steric energy to form symmetrical structure at 1,3-position. This research provides a practical method to produce MLM-type SL from edible oils and fats in food industry.

Transcriptome and Anatomical Comparisons Reveal the Effects of Methyl Jasmonate on the Seed Development of Camellia oleifera.

Seed is a major storage organ that determines the yield and quality of Camellia oleifera (C. oleifera). Methyl jasmonate (MeJA) is a signaling molecule involved in plant growth and development. However, the role of MeJA in the development of C. oleifera seeds remains a mystery. This study demonstrated that the larger seeds induced by MeJA resulted from more cell numbers and a larger cell area in the outer seed coat and embryo at the cellular level. At the molecular level, MeJA could regulate the expression of factors in the known signaling pathways of seed size control as well as cell proliferation and expansion, resulting in larger seeds. Furthermore, the accumulation of oil and unsaturated fatty acids due to MeJA-inducement was attributed to the increased expression of fatty acid biosynthesis-related genes but reduced expression of fatty acid degradation-related genes. CoMYC2, a key regulator in jasmonate signaling, was considered a potential hub regulator which directly interacted with three hub genes (CoCDKB2-3, CoCYCB2-3, and CoXTH9) related to the seed size and two hub genes (CoACC1 and CoFAD2-3) related to oil accumulation and fatty acid biosynthesis by binding to their promoters. These findings provide an excellent target for the improvement of the yield and quality in C. oleifera.

Triterpenoid saponins from Camellia sinensis roots with cytotoxic and immunomodulatory effects.

Camellia sinensis L. (Theaceae) leaves have been used as a beverage in both Eastern and Western cultures for a long time, while its root has not been intensively studied. In this study, seven undescribed triterpenoid saponins (1-7) and twelve known saponins (8-19) with different combinations of substituents, such as oxygenated isoprenyl substituents and sugar moieties, and lengths of sugar chains, were isolated from the C. sinensis roots. Their structures were unequivocally determined using one- and two-dimensional nuclear magnetic resonance data and acid hydrolysis analysis. Investigation of the biological activities of isolated compounds revealed that only those without functional acetyl groups exhibited cytotoxic activities against mouse and human cancer cells (B16F10) and human cervical cancer cell line (HeLa) at 50 µM. Compounds with an aldehyde group at C-23 of aglycone showed immunomodulatory activity against Th1 and Th17 cells at 10 µM. Ten compounds with biological activities from C. sinensis roots extracts, including three previously undescribed ones (3, 6, and 7), were identified.

Five New Oleanane Triterpene Saponins from Camellia petelotii and Their Alpha-glucosidase Inhibitory Activity.

Five new triterpenoid glycosides, named campetelosides A-E (1-5), together with three known compounds, chikusetsusaponin IVa (6), umbellatoside B (7), and silvioside E (8) were isolated from the leaves of Camellia petelotii (Merr.) Sealy. Their chemical structures were determined by interpretations of HR-ESI-MS and NMR spectra. In addition, compounds 1-8 were evaluated for their α-glucosidase inhibitory effects. Compounds 1-3 significantly showed α-glucosidase inhibitory activity with IC50 values of 166.7±6.0, 45.9±2.6, and 395.3±10.5 µM, respectively, compared to that of the positive control, acarbose, with an IC50 value of 200.4±10.5 µM.