Caffeic Research Articles

Magnetic molecularly imprinted polymers using ternary deep eutectic solvent as novel functional monomer for hydroxytyrosol separation

In this work, magnetic molecularly imprinted polymers (MIPs) for specific recognition of Hydroxytyrosol (HT) were designed by vinyl-modified magnetic particles (Fe3O4@SiO2@VTEOs) as carrier, ternary deep eutectic solvent (DES) as functional monomer, while ethylene glycol dimethacrylate (EGDMA) as crosslinker. The optimum amount of DES was obtained by adsorption experiments (molar ratio, caffeic acid: choline chloride: formic acid = 1:6:3) which were 140 μL in total. Under the optimized amount of DES, the maximum adsorption capacity of the MIPs particles was 42.43 mg g−1, which was superior to non-imprinted polymer (4.64 mg g−1) and the imprinting factor (IF) is 9.10. Syringin and Oleuropicrin were used as two reference molecules to test the selectivity of the DES-MIPs particles. The adsorption capacity of HT was 40.11 mg g−1. Three repeated experiments show that the polymer has high stability and repeatability (RSD = 5.50).

High Added-Value by-Products from Biomass: A Case Study Unveiling Opportunities for Strengthening the Agroindustry Value Chain

The current era witnesses a remarkable advancement in biomass utilization, guided by the principles of green chemistry and biorefinery and the comprehensive exploitation of plant-based raw materials. Predominantly, large-scale production methods have been pursued, akin to approaches in the oil industry, enabling the incorporation of novel products into energy and petrochemical markets. However, the viability of such systems on a small and medium scale is hindered by logistical challenges and the constraints of economies of scale. For small agricultural producers and food processing companies, the complete utilization of biomass transcends environmental responsibility, evolving into a strategy for survival through the diversification of by-products with enhanced value. The state of Rio de Janeiro in Brazil presents a range of population dynamics, geographical features, climate conditions, and agricultural production patterns that closely resemble those found in various tropical countries and agricultural regions worldwide. This region, sustaining a green belt supporting 17 million people, provides an apt case study for investigating chemical compounds with potential value among agro-industrial residues, which can motivate the creation of a lucrative biotechnological industry. Examples include naringenin and hesperidin from oranges and lemons, epi-gallo-catechin gallate from bananas, caffeic acids from coffee, and the bromelain enzyme from pineapples. This study addresses the challenges associated with developing biotechnological alternatives within the agroindustry, considering economic, technological, logistical, and market-related aspects. The insights from examining the Brazilian state of Rio de Janeiro will contribute to the broader discourse on sustainable biomass utilization and the creation of value-added by-products.

Phytochemical Screening and Antidiabetic Activity of Aqueous Extract of Evolvulus Alsinoides Leaves: An In Vitro and In Silico Study

ABSTRACT Background: Nowadays, diabetes mellitus has become common worldwide due to changes in lifestyle, sedentary life, alterations in food habits, and other genetic and environmental factors. It is necessary to create awareness about the growing pandemic. Aim: To evaluate the antidiabetic potential of Evolvulus alsinoides. Methods: In vitro α-amylase inhibition and α-glucosidase inhibition activity. Molecular docking analysis. Results: The plant is rich in naturally occurring phytocompound. The results of the study showed that E. alsinoides has the potential to inhibit the activity of alpha-amylase and alpha-glucosidase. Moreover, this result was validated using in silico molecular docking studies that showed a good binding affinity of one of the major phytocompound, caffeic acid, with molecules in the insulin signaling cascade. Conclusion: E. alsinoides has a potent antidiabetic activity and can be further employed in animal and human studies.

Xuebijing injection and its bioactive components alleviate nephrotic syndrome by inhibiting podocyte inflammatory injury

Xuebijing injection (XBJ) is widely used to treat nephrotic syndrome (NS) in clinic, but its bioactive components and therapeutic mechanism are still unclear. In this study, the bioactive components of XBJ were determined by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS). The therapeutic effect of XBJ on NS was evaluated in BALB/c mice induced by adriamycin (ADR, 10 mg/kg) via a single tail vein. The protective effect of XBJ and its bioactive components on podocytes was demonstrated using mouse podocytes (MPC-5) induced by lipopolysaccharide (LPS, 4 μg/mL). The results show that 33 components of XBJ were identified. Furthermore, 12 bioactive components were detected in blood, including protocatechuic acid, salvianolic acid C, benzoyloxypaeoniflorin, danshensu, salvianolic acid A, salvianolic acid B, catechin, caffeic acid, galloylpaeoniflorin, oxypaeoniflorin, hydroxysafflor yellow A, rosmarinic acid. The relative content (%) of the bioactive components were 59.32, 16.01, 9.97, 9.73, 8.72, 8.31, 7.92, 6.54, 1.54, 1.30, 0.68 and 0.59 in this order. After XBJ treatment, the renal function, hyperlipidemia and renal pathological damage were improved in NS model mice. Moreover, the levels of nephrin and desmin which are functional proteins in podocytes were reversed, and the levels of pro-inflammatory factors were reduced by XBJ. Interestingly, protocatechuic acid and salvianolic acid C also showed good protective effects on podocyte function and reduced the level of inflammation in LPS-induced MPC-5. The study is the first time to elucidate the bioactive components of XBJ and its potential therapeutic mechanism for treating NS by protecting podocyte function.

A Polyherbal extract treats Streptozotocin induced Diabetes mellitus: Pharmacognostic study, HPLC analysis and in vivo antidiabetic activity

The plants used in study have been used traditionally for various purposes skin problems, diabetes, astringent, anti-inflammatory, antioxidant, hepatoprotective activities, anthelmintic, antipyretic, antidysentric, anti-hyperlipidemic, anticancer properties. The present study involves the evaluation of pharmacognostic parameters of the four herbal drugs (Azadirachta indica leaves, Pterocarpus marsupium heartwood, Picrorhiza kurroa rhizomes, and Withania coagulans berries and fruit coat), High performance Liquid chromatography (HPLC) as well as antidiabetic activity of polyherbal extract. The qualitative as well as quantitative analysis was done. The drug was given to Streptozotocin induced diabetic rats in doses 250 mg/kg and 500 mg/kg body weight for 21 days. In HPLC analysis it was found that major component in all the extracts was beta carotene along with hesperidin, tannic acid, catechin, ferulic acid, caffeic acid along with other polyphenolic components responsible for the antioxidant activity as well as antidiabetic activity of polyherbal extract. Rats were found to show an increase in body weight, improved blood sugar levels and hemoglobin. The liver glycogen, total proteins, serum lipid profile were restored back to normal range after using the polyherbal extract in diabetic rats. The histopathological study also shows an improvement in diabetic rats at cellular level. The results were found to be dose dependent.

The phenylpropionamide extract of hemp (Cannabis sativa L.) seed improves learning memory ability and survival rate by attenuating microglia activation? and reducing amyloid deposition via the SIRT1-AMAD10 pathway in APP/PS1 mice

Background: Fructus cannabis (Hemp seed), the dried and mature fruit of Cannabis sativa L., was reported to have effects against Alzheimer's disease (AD) in different experimental models. However, either chemical composition or the action of mechanisms was not clear. Our previous work isolated and identified diverse phenylpropionamides such as cannabisin A-F, caffeoyltyramine and feryroyltyramine from hemp seed, which showed antioxidant and anti-neuroinflammatory activity in cells models. Purpose: To study the anti-AD effect and mechanism of the total phenylpropionamides (TPA) extract from hemp seed using APPswe/PS1dE9 mice model. Methods: TPA extract was prepared via extraction and column chromatography techniques, then analyzed and measured using HPLC, HPLC-MS and Folin-Ciocalteu method. The extract was administered by gavage to APPswe/PS1dE9 mice. The learning memory ability of mice were examined using new object recognition test and Morris water maze. Hematoxylin and Eosin staining was used to observe the morphology of neuronal cells in the hippocampal region of brain tissue; ELISA was used to measure the content of IL-1β, TNF-а, IL-6, superoxide dismutase (SOD), malondialdehyde (MDA) in the brain tissue; the deposition of Aβ protein was measured by immunohistochemistry and Western blotting; the activation of microglia was measured by immunofluorescence. The expression of APP, PS1, SIRT1, and ADAM10 proteins was measured by Western blotting. Results: Folin-Ciocalteu method showed the total phenylpropionamide content was 238.03 μg caffeic acid equivalent /mg TPA. HPLC and HPLC-MS analysis showed the contents of N-trans-caffeoyltyramine, cannabisin A and B were 20.16 μg/mg, 32.16 μg/mg and 214.35 μg/mg, respectively, in TPA extract. TPA treatment significantly increased the survival rate of APP/PS1 mice, improved the learning and memory ability, reversed the neural cell damage in the hippocampal region, and reduced Aβ deposition and activated microglia in brain tissue. Meanwhile, the administration decreased the neuroinflammatory factors TNF-α, IL-6, IL-1β expression, increased antioxidant enzyme SOD activity, and attenuated MDA expression. Western blotting showed that TPA administration increased SIRT1 and ADAM10 protein expression and decreased APP and PS1 protein expression. Conclusion: TPA improved learning memory capacity, increased survival, attenuated neuroinflammation, oxidative stress, microglia activation and hippocampal apoptosis, and reduced amyloid deposition via the SIRT1-ADAM10 pathway in APP/PS1 mice.

Anti-COVID-19 Potential of Withaferin-A and Caffeic Acid Phenethyl Ester.

The recent COVID-19 (coronavirus disease 2019) pandemic triggered research on the development of new vaccines/drugs, repurposing of clinically approved drugs, and assessment of natural anti-COVID-19 compounds. Based on the gender difference in the severity of the disease, such as a higher number of men hospitalized and in intense care units, variations in sex hormones have been predicted to play a role in disease susceptibility. Cell surface receptors (Angiotensin-Converting Enzyme 2; ACE2 and a connected transmembrane protease serine 2- TMPSS2) are upregulated by androgens. Conversely, androgen antagonists have also been shown to lower ACE2 levels, implying their usefulness in COVID-19 management. In this study, we performed computational and cell-based assays to investigate the anti-- COVID-19 potential of Withaferin-A and Caffeic acid phenethyl ester, natural compounds from Withania somnifera and honeybee propolis, respectively. Structure-based computational approach was adopted to predict binding stability, interactions, and dynamics of the two test compounds to three target proteins (androgen receptor, ACE2, and TMPRSS2). Further, in vitro, cell-based experimental approaches were used to investigate the effect of compounds on target protein expression and SARS-CoV-2 replication. Computation and experimental analyses revealed that (i) CAPE, but not Wi-A, can act as androgen antagonist and hence inhibit the transcriptional activation function of androgen receptor, (ii) while both Wi-A and CAPE could interact with ACE2 and TMPRSS2, Wi-A showed higher binding affinity, and (iii) combination of Wi-A and CAPE (Wi-ACAPE) caused strong downregulation of ACE2 and TMPRSS2 expression and inhibition of virus infection. Wi-A and CAPE possess multimodal anti-COVID-19 potential, and their combination (Wi-ACAPE) is expected to provide better activity and hence warrant further attention in the laboratory and clinic.

유용미생물에 의한 저이용 산채류의 복합발효 중 생리활성 성분 및 항염증 변화

It was confirmed that complex fermentation (CF) was more efficient than single-strain fermentations in inducing changes in the contents of phenolic compounds of Maclura tricuspidate and Pyrus Montana Nakai. A mixture of Maclura tricuspidata, Pyrus montana Nakai, Platycodon grandiflorum and Codonopsis lanceolata were fermented in CF using Aspergillus shirousamii (koji), yeast, and lactic acid bacteria (LAB) for 24 days, and the pH, °Brix, total acidity, anti-oxidant activity, polyphenol content, nitric oxide (NO), and Western blotting of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) of the sample were determined. There was no significant change in pH and total acidity. °Brix significantly decreased from day 6 onwards. HPLC confirmed that the concentrations of chlorogenic acid, 4-hydrobenzoic acid, vanillic acid, and caffeic acid significantly increased from day 18 during the fermentation. Additionally, DPPH, ABTS radical scavenging activity, total phenol, and total flavonoid were confirmed to be increased until 18 days. NO was significantly inhibited from day 6, along with significant inhibition of iNOS, COX-2, and TNF-a. In conclusion, this study confirmed that CF of low-use (or underutilized) wild vegetables enhances phenolic compounds. It effectively suppresses NO, iNOS, COX-2, and TNF-α, markers of inflammation-related pathogenesis. Altogether, our results suggest that CF of the above plants has a potential anti-inflammatory effect.

Changes in phenolic composition, antioxidant, sensory and microbiological properties during fermentation and storage of maize products

In this study, we assessed the potential of maize (Zea mays) flour to serve as a substrate for the growth, metabolism, and survival of the Fresco culture cocci (Lactococcus lactis ssp. lactis, Lactococcus lactis ssp. cremoris and Streptococcus thermophilus) and Bifidobacterium spp. (B. choerinum K1/1, B. pseudolongum K4/4, B. animalis subsp. animalis J3II, B. thermophilum DSM 20212), which could result in improved nutritional and sensory properties. Maize dairy-free mashes (flavoured with saccharose or caramel) were effectively fermented with Fresco culture for 8 h at 37 °C (3 log increase of counts on average). The functionality of products was proven within the cold storage period (21 days at 6 °C) when viable cell densities of potentially probiotic bacteria were sufficient to demonstrate health-promoting effects (> 5 log CFU/mL). Fermentation process positively changed the contents and compositions of phenolic compounds. Total phenolic content was higher by about 11.5–94.68% in comparison to initial values (0 h). Caffeic acid recorded the highest increase, by about 21.7–151.7%. The antioxidant activity of fermented mashes was also improved. Overall sensory acceptance was enhanced from 2.1 (8 h) to 3.1–3.6 from 4.0 (21 d), which revealed pleasant acceptance of the final caramel products.Graphical

Pomological and Biochemical Characteristics of Local Pomegranate Genotypes of Kahta (Adıyaman) Region

In the study carried out to determine the pomological characteristics of local pomegranate genotypes grown in Kahta district center and Bostanli, Eceler, Balli, Kilisk, Sarica, and Narince villages of Adıyaman province, one orchard belonging to a grower in each region and 1 genotype in each orchard were determined. 10 fruits in each genotype were harvested, and pomological measurements and biochemical analyses were performed. The largest fruit was obtained with the Sarıca genotype and Narince was the genotype with the smallest fruit. In genotypes, the fruit weight was between 196.300-328.909 g, the fruit length 61.528-72.801 mm, and the fruit width between 73.047-86.613 mm. Total aril weight was between 94.144-203.567 g and the fruit volume was between 188.333-327.000. The Sarıca genotype had the highest juice volume and the lowest juice ratio was recorded in the Eceler genotype. Calyx length was longer in the Sarıca genotype and the highest values in terms of calyx radius were recorded with the Kilisk genotype. The Eceler genotype had thicker shells and the Narince genotype had thinner shells. The number of chambers in the genotypes was between 5 and 6. There were significant differences between genotypes in terms of fruit skin and aril color. The soluble solids content (SSC) in genotypes was determined between 12.011-17.267, pH was 3.583-4.073 and total acidity (TA) was 0.736-1.489%. Phenolic compounds such as protocatechuic acid, rutin, gallic acid, chlorogenic acid, epicatechin, ferulic acid, floridzin, vanillic acid, hydroxycinnamic acid, catechin, caffeic acid, syringic acid, and p-coumaric acid were detected in pomegranate fruit, and rutin was phenolic compound with the highest concentration.

Cornelian cherry (Cornus mas L.) as a promising source of antioxidant phenolic substances and minerals

This study aimed to evaluate the mineral content, and content of bioactive compounds in fruits of Cornelian cherry (Cornus mas L.). Neochlorogenic acid, chlorogenic acid, caffeic acid, and rutin were determined in the samples. Vitamin C content ranged from 610.36 to 1344 mg kg−1 FW. Content of K, Ca, P, Mg, and Na in samples ranged from 1750.8 to 2645.7 mg kg−1 FW, from 281.14 to 561.62 mg kg−1 FW, from 180.38 to 294.95 mg kg−1 FW, from 68.19 to 115.43 mg kg−1 FW, and from 2.48 to 71.33 mg kg−1 FW respectively. Content of Fe, Zn, Cu, Mn, Ni, Cr, and Co in samples ranged from 2.77 to 4.88 mg kg−1 FW, from 0.49 to 0.99 mg kg−1 FW, from 0.25 to 0.53 mg kg−1 FW, from 0.07 to 0.17 mg kg−1 FW, from 0.02 to 0.13 mg kg−1 FW, from 0.01 to 0.02 mg kg−1 FW, and from 0.01 to 0.08 mg kg−1 FW respectively. Variations across cultivars were found to be statistically significant, indicating that genetics is a key factor influencing the concentration of bioactive compounds and minerals in Cornelian cherry fruits. Understanding the genetic factors influencing mineral and bioactive compound content in cornelian cherry cultivars is essential for targeted breeding programs, crop improvement, and the development of cultivars with enhanced nutritional and health-promoting attributes. This knowledge contributes to sustainable agriculture and supports the production of crops that align with consumer preferences and health trends.

Effect of Operational Variables on Supercritical Foaming of Caffeic Acid-Loaded Poly(lactic acid)/Poly(butylene adipate-co-terephthalate) Blends for the Development of Sustainable Materials.

Expanded polystyrene will account for 5.3% of total global plastic production in 2021 and is widely used for food packaging due to its excellent moisture resistance and thermal insulation. However, some of these packages are often used only once before being discarded, generating large amounts of environmentally harmful plastic waste. A very attractive alternative to the conventional methods used for polymer processing is the use of supercritical carbon dioxide (scCO2) since it has mass-transfer properties adapted to the foam morphology, generating different path lengths for the diffusion of active compounds within its structure and can dissolve a wide range of organic molecules under supercritical conditions. The objective of this research was to evaluate the effect of operational variables on the process of caffeic acid (CA) impregnation and subsequent foaming of polylactic acid (PLA) as well as two PLA/poly(butylene-co-terephthalate-adipate) (PBAT) blends using scCO2. The results showed an increase in the degree of crystallinity of the CA-impregnated samples due to the nucleation effect of the active compound. On the other hand, SEM micrographs of both films and foams showed significant differences due to the presence of PBAT and its low miscibility with PLA. Finally, the results obtained in this work contribute to the knowledge of the important parameters to consider for the implementation of the impregnation and foaming process of PLA and PLA/PBAT blends with potential use in food packaging.

Acute and subacute toxicological evaluation of the ethanol leaf extract of Morus mesozygia stapf. (Moraceae) in rodents

Ethnopharmacological relevanceTraditionally, the Morus mesozygia tree leaf has been used to manage maladies such as peptic ulcer, hyperglycemia, dermatitis, rheumatism, stomach-ache, arthritis, cough, malignancies, and malaria in parts of Africa. Aim of the studyThe study aimed to evaluate the potential of ethanol leaf extract of Morus mesozygia (EEMm) to induce toxicity by employing both acute and sub-acute oral toxicity experimental models. Material and methodsThe extract's cytotoxicity was studied using brine shrimps (Artemia salina) lethality assay (BSLA), while in the acute toxicity test, male and female mice were administered a single oral dose of EEMm (2000 mg/kg). Male and female Wistar rats received repeated doses of 100 or 500 mg/kg EEMm orally for 28 days in the sub-acute toxicity experiment. The phytochemical analysis of EEMm was done using the HPLC. ResultsThe BSLA revealed a moderate cytotoxic potential of the extract, with an LC50 of 567.13 ± 0.27 μg/mL. All the animals survived the acute toxicity test, with no significant changes in the relative organ weights, suggesting that LD50 is greater than 2000 mg/kg. The animal weights did not vary significantly in the sub-acute toxicity test neither were the alterations in biochemical and hematological tests pronounced, although the histoarchitectures of the kidney, liver and spleen indicated slight anomalies in the evaluated animals. The HPLC analysis revealed the presence of quercetin, ferulic acid, rutin, caffeic acid, morin and gallic acid. ConclusionsEthanol leaf extract of Morus mesozygia demonstrated a safe toxicity profile in rodents, supporting its broad folkloric use in African ethnomedicine.

CAPE ameliorates vascular damage caused by sepsis

parameters of vascular and oxidative damage caused by sepsis and to evaluated the effects of caffeic acid phenethyl ester (CAPE) on these damages.
 Materials and Methods: Wistar-Albino male rats were used for this study. Rats were divided into 4 groups (n = 10). Group 1 animals were intraperitoneally (i.p) injected with sterile saline (Control Group). Group 2 animals were i.p injected with lipopolysaccharide (LPS), 20 mg / kg-weight dose (Sepsis Group). Group 3 animals were i.p injected with lipopolysaccharide, 20 mg / kg-weight dose. Immediately after LPS injection, CAPE was i.p injected at single dose, 10 µmol / kg-body weight (Treatment Group). A single dose of CAPE, 10 µmol / kg-body weight / day, was injected i.p to Group 4 animals for 5 days. After 5th day CAPE injection, a single dose of LPS 20 mg / kg-weight was injected (Protective Group). At the 6th hour after the injections applied to all groups, blood sample were taken intracardiac and their serum were separated for the studies. Homocysteine (Hcy), asymmetric dimethyl arginine (ADMA), endothelin-1 (ET-1) and vascular cellular adhesion molecule-1 (VCAM-1) were measured by enzyme-linked immunosorbent assay (ELISA). In addition, the protective and therapeutic effects of CAPE on these parameters was investigated.
 Results: Control group Hcy, ADMA, ET-1 and VCAM-1 levels were found to be 4.987 ± 0.096 µmol/l, 0.803 ± 0.020 nmol/ml, 21.123 ± 2.575 ng/l, 3.155 ± 0.078 ng/ml, respectively. Sepsis group Hcy, ADMA, ET-1 and VCAM-1 levels were found to be 8.975 ± 0.160 µmol/l, 3.953 ± 0.678 nmol/ml, 52.446 ± 2.546 ng/l, 10.783 ± 1.068 ng/ml, respectively. Treatment group Hcy, ADMA, ET-1 and VCAM-1 levels were found to be 5.286 ± 0.037 µmol/l, 1.304 ± 0.040 nmol/ml, 27.995 ± 1.299 ng/l, 3.72 ± 0.073 ng/ml, respectively. Protective group Hcy, ADMA, ET-1 and VCAM-1 levels were found to be 5.401 ± 0.042 µmol/l, 1.431 ± 0.056 nmol/ml, 32.708 ± 1.326 ng/l, 4.058 ± 0.069 ng/ml, respectively. It was observed that the Hcy, ADMA, ET-1 and VCAM-1 levels of the sepsis group increased significantly compared to the control group (p0.05). It was observed that CAPE treatment significantly decreased these parameters levels. However, the use of CAPE as a protective was not as effective as its treatment effect.
 Conclusion: Our results demonstrated that sepsis resulted in increase Hcy, ADMA, ET-1, VCAM-1 levels. All these changes indicate that sepsis-mediated vascular damage is increased. Our results demonstrated that CAPE is more effective in preventing sepsis-mediated damages when given as a treatment.

The Anti-proliferative Effect of Caffeic Acid and Dactolisib on Human Cervical Carcinoma HeLa Cell Line

Cervical carcinoma is a common gynecological cancer with high mortality rate among women worldwide. Caffeic acid exerts an antiproliferative effect against cervical carcinoma. Dactolisib is a dual PI3K and mTOR inhibitor that has a therapeutic potential for cervical carcinoma. This study aimed to reveal the anti-proliferative effect of combination treatment of caffeic acid and Dactolisib on cervical carcinoma HeLa cell line. Cytotoxicity of caffeic acid and Dactolisib on HeLa cell line was assessed by MTS assay. Colony formation of HeLa cells treated with caffeic acid and Dactolisib was determined by staining colonies with crystal violet and visualizing under light microscope. Dactolisib decreased cell proliferation of HeLa cells in time and dose dependent manner. 5 μM caffeic acid did not show any significant change in cell viability of HeLa cells. Combination treatment of 5 μM caffeic acid and 0.5 μM Dactolisib showed decrease in cell viability of HeLa cells when compared to Dactolisib treated cells. Combination of caffeic acid and Dactolisib decreased colony diameter of HeLa cells significantly when compared to control group. Caffeic acid and Dactolisib shows anti-proliferative effect on human cervical carcinoma HeLa cell line, so further studies should be performed to reveal the mechanism of action.

A study of the protease inhibitory activity component of SARS-CoV-2 3CL in Bletilla striata

The protease Mpro (referred to as 3CLpro or 3CL protease) is a cysteine protease that is highly conserved in coronavirus and is indispensable for viral replication. Because there is no homologous protein for MPro in the human body, SARS-CoV-2 3CL protease is an ideal target against coronavirus. Bletilla striata (Reich. Bf.) is a well-known form of Traditional Chinese Medicine and can exert many pharmacological effects, including hemostasis, anti-microbial and anti-virus activities. Our preliminary screening showed that the n-butanol component of a methanol extract of B. striata exhibited potent inhibitory activity against SARS-CoV-2 3CL protease (58.82% at 200 μg/mL). In this study, we biologically evaluated ten isolated chemical compounds from B. striata and investigated the inhibitory activities of its constituents on SARS-CoV-2 3CL protease. Following bioactivity-guided fractionation, four bibenzyls (1, 4, 6 and 7), three phenols (5, 8 and 9), two anthraquinones (2 and 3) and one glucosyloxybenzyl 2-isobutylmalate (10) were isolated and evaluated for their ability to inhibit SARS-CoV-2 3CL protease by fluorescence resonance energy transfer (FRET) analysis. The binding mode between compounds and enzymes was investigated by molecular docking and Saturation Transfer Differences - nuclear magnetic resonance (STD-NMR). Moreover, Pleiobibenzynin B (7), Blestritin B, Gymconopin D (4), Physcion, 3′-O-methyl dioscin III (6), Gastrodin (8) and caffeic acid (5) all exhibited inhibitory activity against 3CL protease in vitro. The four bibenzyls (1, 4, 6 and 7) exhibited good inhibitory activity against SARS-CoV-2 3CL protease (7.37–39.86 μM). These findings identify potential new inhibitors against SARS-CoV-2 3CL protease, which offers promising lead compounds for the development of novel anti-SARS-CoV-2 drugs.

Effect of pine bark extract and its phenolic compounds on selected pathogenic and probiotic bacterial strains.

Inflammatory bowel disease (IBD) comprises a heterogeneous group of chronic diseases as ulcerative colitis (UC) and Crohn's disease (CD). IBD is the result of a dysregulation of intestinal homeostasis with a host's loss of tolerance toward normal enteric microflora. Plant-based extracts as phenolic compounds can play a role by modulating the intestinal inflammation response. The in vitro antimicrobial activity of French maritime pine bark extract (PBE) and its phenolic constituents has been investigated in this study. Furthermore, the ability of PBE and phenolic compounds (caffeic acid, chlorogenic acid, ferulic acid, gallic acid and taxifolin) to modulate the microbiota has been assessed. Phenolic compounds and PBE showed a great inhibitory effect on the pathogens growth at the highest concentration assessed (1.25 mg/mL). The growth of E. sakazakii and E. faecalis were affected by the effect of caffeic acid and ferulic acid. Taxifolin showed a very strong activity against Listeria sp. (with a reduction ~98%). Gallic acid revealed antibacterial effect on S. aureus at different concentrations. The inhibitory effect of PBE was highly significant on the growth of E. coli O157:H7. PBE, caffeic acid and chlorogenic acid seem to provide the greatest beneficial effect on the probiotic bacteria. However, the highest concentrations of taxifolin may have impaired the growth of beneficial microbiota. Present findings could be of interest for considering PBE and/or its phenolic constituents as protectors against gastrointestinal disturbances which lead to ulcerative colitis and Crohn's disease.

Chemoprofiling and medicinal potential of underutilized leaves of Cyperus scariosus

Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC–MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO3). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.

The Inhibition Mechanisms of Three Structurally Different Salvianolic Acids on the Non-Enzymatic Glycation of Bovine Serum Albumin.

The antiglycation mechanisms of three structurally different salvianolic acids (Sals) including salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and salvianolic acid C (Sal-C) were investigated using the bovine serum albumin (BSA)-fructose model. The results showed that the three compounds could inhibit the formation of glycation products, maintain protein structural stability, mitigate the development of amyloid fibrils and scavenge radicals. Notably, Sal-A possessed the highest anti-glycated activity compared with Sal-B and Sal-C. This may be related to the fact that Sal-A contained the most molecules of caffeic acid (Sal-A, Sal-B, and Sal-C possessing two, one, and zero caffeic acid units, respectively), and caffeic acid played a leading role in the antiglycation properties relative to Danshensu. Moreover, these compounds quenched the intrinsic fluorescence intensity of BSA in a static mode, with the binding constants in the order of Sal-A > Sal-B > Sal-C. Obviously, Sal-A possessed the strongest binding affinity among these compounds, which may be one of the reasons why it exhibited the optimal antiglycation capability. Furthermore, molecular docking demonstrated that the three Sals exerted protective effects on BSA by preventing glycation modification of lysine and arginine residues. These findings would provide valuable insights into the potential application of Sals for alleviating non-enzymatic glycation of protein.

Lithium and sodium 3-(3,4-di-hydroxy-phen-yl)propenoate hydrate.

Treatment of 3-(3,4-di-hydroxy-phen-yl)propenoic acid (caffeic acid or 3,4-di-hydroxy-cinnamic acid) with the alkali hydroxides MOH (M = Li, Na) in aqueous solution led to the formation of poly[aqua-[μ-3-(3,4-di-hydroxy-phen-yl)propenoato]lithium], [Li(C9H7O4)(H2O)]n, 1, and poly[aqua-[μ-3-(3,4-di-hydroxy-phen-yl)propenoato]sodium], [Na(C9H7O4)(H2O)]n, 2. The crystal structure of 1 consists of a lithium cation that is coordinated nearly tetra-hedrally by three carboxyl-ate oxygen atoms and a water mol-ecule. The carboxyl-ate groups adopt a μ3-κ3 O:O':O' coordination mode that leads to a chain-like catenation of Li cations and carboxyl-ate units parallel to the b axis. Moreover, the lithium carboxyl-ate chains are connected by hydrogen bonds between water mol-ecules attached to lithium and catechol OH groups. The crystal structure of 2 shows a sevenfold coordination of the sodium cation by one water mol-ecule, two monodentately binding carboxyl-ate groups and four oxygen atoms from two catechol groups. The coordination polyhedra are linked by face- and edge-sharing into chains extending parallel to the b axis. The chains are inter-linked by the bridging 3-(3,4-di-hydroxy-phen-yl)propenoate units and by inter-molecular hydrogen bonds to form the tri-periodic network.