Veronica linariifolia subsp. dilatata ameliorates LPS-induced acute lung injury by attenuating endothelial cell barrier dysfunction via EGFR/Akt/ZO-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried aerial parts of Veronica linariifolia subsp. dilatata (Nakai & Kitag.) D.Y.Hong named Shui Man Jing (SMJ) is a traditional Chinese medicine with a long history of clinical use in the treatment of chronic bronchitis and coughing up blood, however, its role on acute lung injury (ALI) has not been revealed yet. AIM OF THE STUDY: To assess the efficiency of SMJ on ALI and to investigate whether it inhibited endothelial barrier dysfunction by regulating the EGFR/Akt/ZO-1 pathway to alleviate ALI in vivo and in vitro based on the result of network pharmacology. MATERIALS AND METHODS: An in vivo model of ALI was established using inhalation of atomized lipopolysaccharide (LPS), and the effects of SMJ on ALI were evaluated through histopathological examination and inflammatory cytokines, lung histology and edema, vascular and alveolar barrier disruption. Network pharmacology was applied to predict the mechanism of SMJ in the treatment of ALI. The crucial targets were validated by RT-PCR, Western Blotting, molecular docking, immunohistochemistry and immunofluorescence methods in vivo and in virto. RESULTS: Administration of SMJ protected mice against LPS-induced ALI, including ameliorating the histological alterations in the lung tissues, and decreasing lung edema, protein content of bronchoalveolar lavage fluid, infiltration of inflammatory cell and secretion of cytokines. SMJ exerted protective effects in ALI by inhibiting endothelial barrier dysfunction in mice and bEnd.3 cell. SMJ relieved endothelial barrier dysfunction induced by LPS through upregulating the EGFR expression. SMJ also increased the phosphorylation of Akt, and ZO-1 expression both in vivo and in vitro. CONCLUSION: SMJ attenuates vascular endothelial barrier dysfunction for LPS-induced ALI via EGFR/Akt/ZO-1 pathway, and is a promising novel therapeutic candidate for ALI.

Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation.

Excess acetaminophen (APAP) commonly causes severe acute liver injury (ALI), characterized by oxidative stress, pro-inflammatory responses, and hepatocyte damage. Veronica persica (VP) is a traditional medicine with antioxidant and anti-inflammatory properties. There is a paucity of information on its medicinal value, especially its potential mechanisms for alleviating ALI. This study aimed to clarify the ameliorative effects and intracellular mechanisms of VP on APAP-induced ALI via attenuating oxidative stress and inflammation. Mice were given VP for 7 days before exposure to APAP (300 mg/kg). The HPLC and radical scavenging assay found that VP contains 12 phenolic acids and 6 flavonoids, as well as show robust antioxidant capacity. In the APAP-induced ALI model, pre-treatment with VP significantly reduces APAP-induced hepatotoxicity by observing improved hepatocyte pathological injury and further confirmed by serum biochemical indicator. Also, the reduction of TUNEL-positive regions and the regulation of Bcl-2-associated X protein indicated that VP attenuates hepatocytotoxicity. Moreover, VP pre-intervention inhibits the formation of liver pro-inflammatory cytokines, the expression of inflammatory response genes, and increases in myeloperoxidase (MPO) in APAP-exposed mice. The elevated reduced glutathione (GSH) levels and decreased oxidative stress markers indicate that VP reduces APAP-promoted oxidative stress. Further study revealed that VP inhibited the phosphorylation of NF-κB/STAT3 cascade, blocked ERK and JNK phosphorylation, and activated AMP-activated protein kinase (AMPK). To sum up, this study demonstrated that VP exists hepatoprotective abilities on APAP-induced ALI, primarily by suppressing the phosphorylation of NF-κB/STAT3 cascade and ERK-JNK and inducing AMPK activation to alleviate oxidative stress and inflammation.

Isolation of Volatile Compounds by Microwave-Assisted Extraction from Six Veronica Species and Testing of Their Antiproliferative and Apoptotic Activities.

This study was conducted to determine the differences in the chemical composition of the essential oils and hydrosols of six different Veronica species (V. agrestis, V. anagalloides, V. austriaca ssp. jacquinii, V. beccabunga, Veronica cymbalaria, and V. officinalis) and to test their antiproliferative and apoptotic activities, according to the authors' knowledge, because of insufficient research and lack of information. Also, the goal was to determine which obtained samples were better in achieving antiproliferative and apoptotic activities and due to which volatile components. Therefore, essential oils (EOs) and hydrosols (HYs) were isolated from the above-mentioned Veronica species by microwave-assisted extraction (MAE). Phytochemical identification of the free volatile compounds was performed using a GC equipped with a flame ionization detector and a mass spectrometer. Their antiproliferative and apoptotic activities against two human cancer cell lines, breast cancer cell line MDA-MB-231 and bladder cancer cell line T24, were determined. The main compounds identified in the studied Veronica EOs and HYs were terpinen-4-ol (0.34-6.49%), linalool (0.34-6.61%), (E)-caryophyllene (0.97-7.55%), allo-aromadendrene (0.18-2.21%), caryophyllene oxide (1.42-23.83%), benzene acetaldehyde (0.26-13.34%), and ß-ionone (1.08-16.53%). In general, HYs of the tested Veronica species showed higher antiproliferative activity (IC50 13.41-42.05%) compared to EOs (IC50 158.1-970.4 µg/mL) on MDA-MB-231 and T24 cancer cell lines after 48 and 72 h. V. agrestis EO showed the best apoptotic effect among the EOs on the MDA-MB-231 cancer cell line (10.47 ± 0.53% and 9.06 ± 0.74% of early/late apoptosis, compared with control 3.61 ± 0.62% and 0.80 ± 0.17% of early/late apoptosis, respectively) and among the HYs V. cymbalaria showed 9.95 ± 1.05% and 3.06 ± 0.28% of early/late apoptosis and V. anagalloides 8.29 ± 1.09% and 1.95 ± 0.36% of early/late apoptosis compared with control (for EO was 7.45 ± 1.01% and 0.54 ± 0.25%, and for HY was 4.91 ± 1.97% and 0.70 ± 0.09% of early/late apoptosis, respectively) on the T24 cancer cell line. Future research will include other Croatian species of the genus Veronica to gain a more complete insight into the biological activity of the volatile products of this genus for potential discovery of drugs based on natural plant extracts.

Efficacy of Veronica incana for Treating Osteoarthritis Induced by Monosodium Iodoacetate in Rats.

The aim of this study is to investigate the efficacy and the underlying mechanism of Veronica incana in osteoarthritis (OA) induced by intraarticular injection of monosodium iodoacetate (MIA). The selected major four compounds (A-D) of V. incana were found from fractions 3 and 4. Its structure elucidation was determined by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) data analysis and nuclear magnetic resonance (NMR) data comparison with literature. MIA (50 µL with 80 mg/mL) for the animal experiment was injected into the right knee joint. The V. incana was administered orally every day to rats for 14 days from 7 days after MIA treatment. Finally, we confirmed the four compounds: (A) verproside; (B) catalposide; (C) 6-vanilloylcatapol; and (D) 6-isovanilloylcatapol. When we evaluated the effect of V. incana on the MIA injection-induced knee OA model, there were a noticeable initial decreased in hind paw weight-bearing distribution compared to the Normal group (P < .001), but V. incana supplementation resulted in a significant increase in the weight-bearing distribution to the treated knee (P < .001). Moreover, the V. incana treatment led to a decrease in the levels of liver function enzymes and tissue malondialdehyde (P < .05 and .01). The V. incana significantly suppressed the inflammatory factors through the nuclear factor-kappa B signaling pathway and downregulated the expression of matrix metalloproteinases, which are involved in the degradation of the extracellular matrix (P < .01 and .001). In addition, we confirmed the alleviation of cartilage degeneration through tissue stains. In conclusion, this study confirmed the major four compounds of V. incana and suggested that V. incana could serve as an anti-inflammatory candidate agent for patients with OA.

Characterization of the complete chloroplast genome of Veronica arvensis and its phylogenomic inference in plantaginaceae.

Veronica arvensis, which is an annual flowering plant in the plantain family Plantaginaceae, has commonly used as a Chinese herbal medicine to treat malaria in China. Here, the complete plastome of V. arvensis was successfully assembled based on genome skimming sequencing. The plastome of V. arvensis was 149,386 bp in length, comprising a pair of inverted repeats (IR; 24,946 bp) separated by a large single-copy (LSC) region (82,004 bp) and a small single-copy (SSC) region (17,490 bp). The plastid genome encoded 113 unique genes, consisting of 79 protein-coding genes, 30 tRNA genes, and four rRNA genes, with 19 duplicated genes in the IR regions. Six plastid hotspot regions (trnH-psbA, trnK-rps16, atpI-rps2, ndhF-rpl32, ccsA-ndhD and rps15-ycf1) were identified within Veronica. Phylogenetic analysis showed that the representative species from Veronica was monophyletic. V. persica and V. polita formed a maximum clade, followed by sister to V. arvensis.

Characterization of the complete chloroplast genome of the medicinal herb Veronica polita Fr. 1819 (Lamiales: Plantaginaceae).

Veronica polita Fr. 1819 (synonym: Veronica didyma Ten. 1981) is a species of annual herb with high medicinal value. It is originally from Southwest Asia, but has been naturalized widely in many regions of the world. In this study, the complete chloroplast genome of V. polita was determined to be 150,191 bp long with a typical quadripartite structure, comprising two inverted repeat regions (IRa and IRb, 25,465 bp each), a large single-copy (LSC) region (81,847 bp) and a small single-copy (SSC) region (17,414 bp). It encodes a panel of 114 genes (including 79 protein-coding, 31 tRNA, and four rRNA genes) with 18 of them being completely or partially duplicated and 19 of them possessing one or two introns. Phylogenetic analysis supported the tribal-level taxonomy of the family Plantaginaceae, and revealed that V. polita was most closely related to the congener Veronica persica Poir. 1808.

Characterization of the complete plastid genome of of Veronica eriogyne H. Winkl., a Tibetan medicinal herb.

Veronica eriogyne H. Winkl.(Plantaginaceae) is a perennial herb with high medicinal value. To better understand the molecular genetics and evolutionary of V. eriogyne, its complete plastid genome was sequenced and annotated. The assembled chloroplast genome is a circular 151,083 bp sequence, consisting of a 82,302 bp large single copy region (LSC) and a 17,449 bp small single copy region (SSC), which were flanked by a pair of 25,666 bp inverted repeats (IRs). The GC content of the chloroplast genome is 38.03%. Moreover, a total of 134 functional genes were annotated, including 88 protein-coding, 38 tRNA, and 8 rRNA genes. Phylogenetic analysis showed that V. eriogyne has close relationship with V. persica Poi. The current study provides important information for further genetic studies on Plantaginacea.

The protective effect of Veronica ciliata Fisch. Extracts on relieving oxidative stress-induced liver injury via activating AMPK/p62/Nrf2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Veronica ciliata Fisch. existed in various Tibetan medicine prescriptions, which was recorded to treat liver diseases in the Tibetan medicine roll of Chinese materia medica. HYPOTHESIS/PURPOSE: The current study aimed to examine the effect of active constituents from V.ciliata relieving oxidative stress-mediated liver injury and clarify the underlying mechanism. MATERIALS AND METHODS: tert-Butyl hydroperoxide (BHP) induced liver injury in mice model was established to evaluate the hepatoprotective effect of ethyl acetate extract of V. ciliata (EAFVC). Serum and liver indicators, as well as the histopathological change of liver were examined. Next, the constituents of EAFVC were separated and characterized by high-speed countercurrent chromatography (HSCCC) and Ultra performance liquid chromatography-mass spectrometer (UPLC-MS), respectively. Based on the above, the antioxidant activity of EAFVC and two fractions was evaluated using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azino-bis (3-ethylbenzothiazoli- ne-6-sulfonic acid) (ABTS) free radical scavenging assays. The hepatoprotective activity of EAFVC and its fractions/compounds attenuating ethanol-induced hepatocyte damage in BRL-3A cells was evaluated using the MTT method. The effect of the fraction and compounds with the strongest protective activity on ethanol-induced cytotoxicity, reactive oxygen species (ROS) accumulation, and glutathione (GSH) depletion was investigated. mRNA expression of nuclear factor-E2-related factor 2 (Nrf2) and nuclear factor of κB (NF-κB), as well as their downstream target genes, was determined by RT-qPCR. Finally, the potential mechanism of fraction 1 and luteolin on the AMPK/p62/Nrf2 signal pathway was studied using western blotting. RESULTS: Firstly, EAFVC could relieve liver impairment induced by t-BHP in mice. Next, fraction 1 enriched with polyphenolic compounds and luteolin derived from EAFVC were screened to yield the highest hepatoprotective activity against ethanol-induced hepatocyte damage. Further study demonstrated that fraction 1 and luteolin relieved BRL-3A cells damage by decreasing the aspartate aminotransferase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) activities, ROS accumulation, as well as the depletion of GSH. Also, we determined that fraction 1 and luteolin suppressed inflammation and apoptosis of BRL-3A cells. The mechanistic studies indicated that fraction 1 could attenuate oxidative stress, inflammation, and apoptosis by activating AMPK phosphorylation, which promotes autophagy associated protein expression (LC3-B, Beclin1 and p62) as well as promote phosphorylation of p62 -dependent autophagic degradation of Keap1, to induce Nrf2 dissociation from Keap1 and translocate to nuclear. Nrf2 in the nuclear activate cytoprotective related genes to exert hepatoprotective function. Finally, we found that luteolin activated the protein expression of p-AMPK, p-p62, p62, Nrf2, and its downstream target genes. CONCLUSIONS: This study clarified that fraction 1 enriched phenolic compounds could attenuate ethanol-induced liver injury in BRL-3A cells via activating AMPK/p62/Nrf2 pathway. Luteolin could serve as the major bioactive component in the therapeutic effect of fraction 1. These active constituents in V. ciliata could be used as the potential drugs targeted activation of AMPK or p62 for relieving oxidative stress-mediated liver disorders.

Protective effects of n-Butanol extract and iridoid glycosides of Veronica ciliata Fisch. Against ANIT-induced cholestatic liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Veronica ciliata Fisch. is a traditional medical herb that present in more than 100 types of Tibetan medicine prescriptions, most of which are used for liver disease therapy. Iridoid glycosides have been identified as the major active components of V.ciliata with a variety of biological activities. AIMS OF THE STUDY: The aim of this study is to explore the protective effect and potential mechanism of n-Butanol extract (BE) and iridoid glycosides (IG) from V.ciliata against ɑ-naphthyl isothiocyanate (ANIT)-induced hepatotoxicity and cholestasis in mice. MATERIALS AND METHODS: Mice were intragastrically (i.g.) given BE and IG at different dose or positive control ursodeoxycholic acid (UCDA) once a day for 14 consecutive days, and were treated with ANIT to cause liver injury on day 12th. Serum levels of hepatic injury markers and cholestasis indicators, liver index and liver histopathology were measured to evaluate the effect of BE and IG on liver injury caused by ANIT. The protein levels of tumor necrosis factor-α (TNF-α), nuclear factor kappa B(NF-κB), interleukin-6 (IL-6), Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), and the levels of oxidative stress indicators in liver tissue were investigated to reveal the underlying protective mechanisms of BE and IG against ANIT-induced hepatotoxicity and cholestasis. RESULTS: The n-Butanol extract (BE) and iridoid glycosides (IG) isolated from V.ciliata significantly decreased serum level of cholestatic liver injury markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bile acid (TBA), total bilirubin (TBIL), and direct bilirubin (DBIL) in ANIT-treated mice. Histopathology of the liver tissue showed that pathological damages were relieved upon BE and IG treatment. Meanwhile, the results indicated BE and IG notably restored relative liver weights, inhibited oxidative stress induced by ANIT through increasing hepatic level of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and decreasing hepatic content of malondialdehyde (MDA). Western blot revealed that BE and IG inhibited the expression of pro-inflammatory factors TGF-α, IL-6 and NF-κB. Furthermore, the decreased protein expression of bile acid transporters NTCP, BSEP, MRP2 were upregulated by BE and IG in a dose-dependent manner. CONCLUSION: The results have demonstrated that BE and IG exhibited a dose-dependently protective effect against ANIT-induced liver injury with acute intrahepatic cholestasis in mice, which might be related to the regulation of oxidative stress, inflammatory response and bile acid transport. In addition, these findings pointed out that iridoid glycosides as main active components of V.ciliata play a critical role in hepatoprotective effect of V.ciliata.

Veronica austriaca L. Extract and Arbutin Expand Mature Double TNF-α/IFN-γ Neutrophils in Murine Bone Marrow Pool.

Plants from the Veronica genus are used across the world as traditional remedies. In the present study, extracts from the aerial part of the scarcely investigated Veronica austriaca L., collected from two habitats in Bulgaria-the Balkan Mountains (Vau-1) and the Rhodopi Mountains (Vau-2), were analyzed by nuclear magnetic resonance (NMR) spectroscopy. The secondary metabolite, arbutin, was identified as a major constituent in both extracts, and further quantified by high-performance liquid chromatography (HPLC), while catalpol, aucubin and verbascoside were detected at lower amounts. The effect of the extracts and of pure arbutin on the survival of neutrophils isolated from murine bone marrow (BM) were determined by colorimetric assay. The production of cytokines-tumor necrosis factor (TNF)-α and interferon (IFN)-γ was evaluated by flowcytometry. While Vau-1 inhibited neutrophil vitality in a dose-dependent manner, arbutin stimulated the survival of neutrophils at lower concentrations, and inhibited cell density at higher concentrations. The Vau-1 increased the level of intracellular TNF-α, while Vau-2 and arbutin failed to do so, and expanded the frequency of mature double TNF-α+/IFN-γhi neutrophils within the BM pool.

Phenols fragment of Veronica ciliata Fisch. ameliorate free radical-induced nonalcoholic fatty liver disease by mediating PI3K/Akt signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Veronica ciliata Fisch. is used in numerous of Tibetan medicine prescriptions because of its hepatoprotective effect. AIMS OF THIS STUDY: Here, we aimed to investigate the hepatoprotective effect and mechanism of phenolic fraction (PF) of V. ciliata Fisch. on liver injury induced by free radical. MATERIALS AND METHODS: BRL 3A cells were pre-treated with PF and luteolin (Lut) following tert-butyl hydroperoxide (t-BHP) treatment. The cell viability, lactate dehydrogenase (LDH) levels, reactive oxygen species (ROS) generation, apoptosis, cell cycle and autophagy were analyzed. Apoptotic, inflammatory, and autophagy,- related proteins were analyzed using Western blotting. The combination of molecular docking and drug affinity targeting experiments (DARTS) were first utilized to analysis the target protein of Lut. RESULTS: PF effectively suppressed t-BHP-induced apoptosis caused by mitochondrial dysfunction, which were associated with inhibiting ROS generation. Further investigation indicated that PF significantly suppressed apoptosis, inflammation, and autophagy by regulating the expression of related proteins. The results of molecular docking and drug affinity targeting experiments (DARTS) revealed that PI3K was the target protein of PF and Lut. Further studies have shown that PF relieved liver injury induced by t-BHP via suppressing phosphorylated expression of PI3K. CONCLUSION: Our results indicate that PF effectively protect against hepatotoxicity induced by t-BHP through inhibiting the abnormal activation of PI3K-Akt signaling pathway and highlight the health benefits of PF regarding oxidative stress, proving it to be an important source of bioactive compounds associated with Nonalcoholic fatty liver disease (NAFLD).

Review of the Ethnopharmacology, Phytochemistry, and Pharmacology of the Genus Veronica.

Veronica is the largest genus in the flowering plant family Plantaginaceae and comprises approximately 500 species. The genus was formerly placed in the Scrophulariaceae family, some species of which have been used in traditional medicine for the treatment of influenza, respiratory diseases, hemoptysis, laryngopharyngitis, cough, hernia, cancer, edema, and wounds. This review comprehensively summarizes the current information on the traditional uses, phytochemistry, and pharmacology of the genus Veronica on the basis of articles published from 1970 to 2018. More than 260 compounds have been isolated, and chemotaxonomic investigations of Veronica have revealed that iridoid glucosides - including aucubin, catalpol, and 6-O-catalpol derivatives - are characteristic of this genus. Modern pharmacological studies and clinical practice have demonstrated that extracts or monomeric compounds from Veronica have several pharmacological actions, such as anti-inflammatory, anti-oxidative, anticancer, antibacterial, anti-angiogenic, antineurodegenerative, neuroprotective, and hepatoprotective effects both in vivo and in vitro.

Phytochemical composition, isolation and hepatoprotective activity of active fraction from Veronica ciliata against acetaminophen-induced acute liver injury via p62-Keap1-Nrf2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Veronica ciliata Fisch, a traditional Tibetan medicine, used to cure hepatitis and existed in lots of Tibetan medicine prescriptions owing to its hepatoprotective activity. AIMS OF THIS STUDY: In this study, we are aimed to systematically analysis and isolate the chemical constituents of the ethyl acetate fraction from V. ciliata (EAFVC), and test the hepatoprotective effect and mechanism of EAFVC and its compounds on attenuating the liver injury induced by acetaminophen (APAP) in vivo and vitro. MATERIALS AND METHODS: UPLC-PDA-ESI-MS method was established for the analysis of the components in EAFVC, which was further separated using multiple chromatographic techniques. The MS, 1H and 13C NMR were applied to elucidate their structures. UPLC-PDA method was applied for the simultaneous quantification of major compounds of EAFVC. Furthermore, the protective effect of the EAFVC was determined using APAP-induced acute hepatotoxicity in mice and BRL-3A cells model, respectively. In addition, the hepatoprotective activity of two main compounds in EAFVC on relieving APAP-induced liver injury was further evaluated. Finally, we have some concerns about the protective mechanism of EAFVC via enzyme-linked immunosorbent assay (ELISA), reactive oxygen species (ROS) detection, quantitative real-time PCR (qPCR), western blot analysis and molecular docking. RESULTS: Thirteen compounds were successfully identified using UPLC-PDA-ESI-MS for the first time. Meanwhile, other twelve compounds were separated from EAFVC. Eventually, twenty-five compounds were successfully identified from the EAFVC. Among these compounds, fourteen compounds (3, 8, 10, 14-17, 19-25) were separated from V.ciliata for the first time. In addition, UPLC-PDA analysis method was first to establish for simultaneous determination of the main compounds (1, 2, 4, 5, 7, 9, 12). Further assay indicated that the liver injury in mice induced by APAP showed a significant reversal by EAFVC, as evidenced by reducing the activities of liver function enzymes, suppressing the lipid peroxidation as well as increasing the serum total antioxidant capacity (T-AOC) and the activities of antioxidant enzymes. Pathological sections showed that the liver in the high dose has significant improvement in mice. In vitro experiment also showed that EAFVC elevate the viability, inhibiting the activities of liver function enzymes as well as the generation of ROS of BRL-3A cells. In addition, Catalposide and verproside could reverse the low cell viability of BRL-3A cells induced by APAP. The mechanism research in vitro demonstrated that EAFVC could promote the mRNA and protein expression of heme oxygenase-1 (HO-1), NAD(P) H dehydrogenase quinone 1 (NQO-1) and catalytic or modify subunit of glutamate-cysteine ligase (GCLC/GCLCM) via enhancing nuclear factor-E2-related factor 2 (Nrf2) and p62/SQSTM1 (p62) expression in protein level. Molecular docking results demonstrated that catalposide and verproside have strong affinity to the kelch-like ECH-associated protein-1(Keap1) Kelch domain. CONCLUSION: This research is the first to clarify the substance basis of the hepatoprotective activity of the EAFVC and provide the further scientific data for the traditional use of this Tibetan Medicine. EAFVC is valuable to be further investigated as active preparations for application in liver protection via activating p62- Keap1-Nrf2 pathway.

Veronica Plants-Drifting from Farm to Traditional Healing, Food Application, and Phytopharmacology.

The Veronica genus, with more than 200 species, belongs to the Plantaginaceae family and is distributed over most of the Northern Hemisphere and in many parts of Southern Hemisphere. These plants are traditionally used in medicine for wound healing, in the treatment of rheumatism, and in different human diseases. This paper reviews the chemical composition of some valuable Veronica species, the possibilities Veronica extracts have in food preservation and as food ingredients, and their functional properties. Veronica species represent a valuable source of biological active secondary metabolites, including iridoid glycosides and phenolic compounds. In particular, due to presence of these phytochemicals, Veronica species exhibit a wide spectrum of biological activities, including antimicrobial and antioxidant. In fact, some studies suggest that some Veronica extracts can inhibit foodborne pathogens, such as Listeria monocytogenes, but only a few of them were performed in food systems. Moreover, anticancer, anti-inflammatory, and other bioactivities were reported in vitro and in vivo. The bioactivity of Veronica plants was demonstrated, but further studies in food systems and in humans are required.

Regulation of JAK2/STAT3 and NF-κB signal transduction pathways; Veronica polita alleviates dextran sulfate sodium-induced murine colitis.

Ulcerative colitis (UC) is a major inflammatory bowel disease (IBD) has become a worldwide emergent disease. Veronica polita (VP) is a medicinal herb that has strong antioxidant and anti-inflammatory properties. In the present study, we studied the protective effect of VP on dextran sulfate sodium (DSS)-induced experimental colitis in mice. Phytochemical screening of VP extract demonstrated the presence of high total phenolic and flavonoid contents. Compared with the DSS group, VP significantly reduced clinical symptoms with less weight loss, bloody stool, shortening of the colon, and the severity of colitis was considerably inhibited as evidenced by the reduced disease activity index (DAI) and degree of histological damage in the colon and spleen. Also, treatment with VP considerably decreased the nitric oxide (NO) and malondialdehyde (MDA) level. VP remarkably downregulated the expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), inducible nitric oxide synthetase (iNOS) and cyclooxygenase-2 (COX-2) in the colon tissue. Likewise, activation of the signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-κB) was effectively blocked by VP. Taken together, these results demonstrate that VP has an ameliorative effect on colonic inflammation mediated by modulation of oxidative stress and inflammatory mediators by suppressing the JAK2/STAT3 and NF-κB signaling pathways.

Mitodepressive, antioxidant, antifungal and anti-inflammatory effects of wild-growing Romanian native Arctium lappa L. (Asteraceae) and Veronica persica Poiret (Plantaginaceae).

The present study aims to evaluate the potential uses of hydroalcoholic extracts obtained from Romanian native wild-growing plants. The hydroalcoholic extracts were obtained from the burdock roots and respectively the aerial parts of birdeye speedwell. The extracts were characterised by HPLC (quantifying 13 compounds in the V. persica extract, 6 compounds in the A. lappa extract and confirming the presence of arctiin and arctigenin in the burdock extract). The antioxidant potential of the crude extracts was evaluated using two methods: the DPPH assay (79.91% for speedwell extract, 76.23% for burdock extract) and the phosphomolybdate method (296.5 mg/g ascorbic acid equivalents for burdock, 324.4 mg/g for speedwell). The crude extracts were found to be active against both fungal lines used (Aspergillus niger and Penicillium hirsutum), inhibition zones - 17.1 mm and 13.1 mm against P. hirsutum, respectively ca. 22 mm for both extracts against A. niger. The cytogenetic effects (assessed using the Allium cepa assay) revealed a series of chromosomal aberrations and nuclear aberrations induced in the meristematic root cells. The anti-inflammatory effect, estimated in two inflammation experimental models, showed a significant effect, especially for the speedwell extract. The results recommend the evaluated extracts as promising sources of biologically-active compounds.

Veronica officinalis Product Authentication Using DNA Metabarcoding and HPLC-MS Reveals Widespread Adulteration with Veronica chamaedrys.

Studying herbal products derived from local and traditional knowledge and their value chains is one of the main challenges in ethnopharmacology. The majority of these products have a long history of use, but non-harmonized trade and differences in regulatory policies between countries impact their value chains and lead to concerns over product efficacy, safety and quality. Veronica officinalis L. (common speedwell), a member of Plantaginaceae family, has a long history of use in European traditional medicine, mainly in central eastern Europe and the Balkans. However, no specified control tests are available either to establish the quality of derived herbal products or for the discrimination of its most common substitute, V. chamaedrys L. (germander speedwell). In this study, we use DNA metabarcoding and high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) to authenticate sixteen V. officinalis herbal products and compare the potential of the two approaches to detect substitution, adulteration and the use of unreported constituents. HPLC-MS showed high resolution in detecting phytochemical target compounds, but did not enable detection of specific plant species in the products. DNA metabarcoding detected V. officinalis in only 15% of the products, whereas it detected V. chamaedrys in 62% of the products. The results confirm that DNA metabarcoding can be used to test for the presence of Veronica species, and detect substitution and/or admixture of other Veronica species, as well as simultaneously detect all other species present. Our results confirm that none of the herbal products contained exactly the species listed on the label, and all included substitutes, contaminants or fillers. This study highlights the need for authentication of raw herbals along the value chain of these products. An integrative methodology can assess both the quality of herbal products in terms of target compound concentrations and species composition, as well as admixture and substitution with other chemical compounds and plants.

HSCCC Separation of the Two Iridoid Glycosides and Three Phenolic Compounds from Veronica ciliata and Their in Vitro Antioxidant and Anti-Hepatocarcinoma Activities.

Five main compounds, including two iridoid glycosides (catalposide, verproside) and three phenolic compounds (luteolin, 4-hydroxy benzoic acid, 3,4-dihydroxy benzoic acid), were separated and prepared from the crude extract of Veronica ciliata by high-speed countercurrent chromatography. n-Hexane/n-butanol/water (1.5:5:5, v/v/v) was used for the separation of catalposide and verproside. n-Hexane/n-butanol/water (3:2:5, v/v/v) was used for the separation of luteolin, 4-hydroxy benzoic acid and 3,4-dihydroxy benzoic acid. The head-to-tail elution mode was used with a flow rate of 5.0 mL/min and a rotary speed of 800 rpm. Finally, a total of 1.28 mg luteolin, 6 mg 4-hydroxy benzoic acid, 2 mg 3,4-dihydroxy benzoic acid, 2 mg verproside and 10 mg catalposide with purities of 98%, 99.1%, 99.5%, 99.8% and 99%, respectively, were obtained from 200 mg of crude extract. In addition, their structure was identified using MS, ¹H-NMR and (13)C-NMR. To the best of our knowledge, this is the first report of the separation and purification of iridoid glycosides and phenolic compounds from V. ciliata by high-speed countercurrent chromatography (HSCCC). Among these compounds, luteolin, 4-hydroxy benzoic acid and 3,4-dihydroxy benzoic acid were separated from V. ciliata Fisch. for the first time. The results of the antioxidant activity show that protocatechuic acid and luteolin have strong antioxidant activity compared to 2,6-di-tert-butyl-4-methylphenol (BHT) and vitamin C (Vc). Five compounds also exhibited strong anti-hepatocarcinoma activities.

Bioactivity-guided isolation of antioxidant and anti-hepatocarcinoma constituents from Veronica ciliata.

BACKGROUND: Veronica ciliata Fisch., widely distributed in western China, has been traditionally used in Tibetan Medicine as a treatment for hepatitis, cholecystitis, rheumatism, and urticaria. However, V. ciliata Fisch. has not been subjected to detailed chemical constitution analysis and the bioactive studies were restricted to its crude extracts. It is necessary to investigate the active chemical components of these extracts and identify their biological effects. RESULTS: Four iridoid glycosides, (veronicoside, cataposide, amphicoside, and verminoside) were isolated from the ethyl acetate fraction. Among these compounds, veronicoside and verminoside were isolated for the first time from this plant. These compounds exhibited strong antioxidant activity and inhibitory activity on HepG2 cell proliferation. The antioxidant activity of verminoside was equal to Vc. Cataposide, amphicoside and verminoside had stronger anti-hepatocarcinoma activity than 5-fluorouracil. CONCLUSIONS: Four iridoid glycosides,(veronicoside, cataposide, amphicoside and verminoside) were isolated from the extract of V. ciliata Fisch. using bioassay-guided screening.Among these compounds, veronicoside and verminoside were isolated for the first time from this plant. The above results indicated that these compounds were the active chemical components responsible for the antioxidant and anti-hepatocarcinoma properties of V. ciliata Fisch. The underlying mechanism of their bioactivity is worthy of further investigation. Graphical abstractBioactivity-guided isolation of antioxidant and anti-hepatocarcinoma constituents from Veronica ciliata.

Selenium and its compounds in aquatic plant Veronica anagallis-aquatica.

The uptake, distribution and determination of Se and its compounds in macrophyte Veronica anagallis-aquatica were investigated. V. anagallis-aquatica and sediments were sampled in years 2009-2011 and in 2013 in three Slovenian watercourses flowing through an agricultural area, where addition of Se in feedstuffs has been performed for about 25 years. Se content in sediments were up to 0.86 µg g(-1) and in whole plant varied from 0.186 to 1.535 µg g(-1), all on dry weight basis. Se content were measured also in different plant parts; highest content were found in roots and lowest in stems. Separation of extractable Se compounds was performed by ion exchange chromatography and for on-line detection inductively coupled plasma-mass spectrometry was used. The results showed that only approximately 24% of Se in the macrophyte was extracted using enzyme Protease XIV. Extractable Se in plant parts varied from 10.5% in roots to 29.6% in leaves. Identification of Se(IV) and Se(VI) was achieved but no Se-amino acids were detected even at highest Se content. According to our results, we assume that 25 years of Se addition in feedstuff shows minimal impact on Se content in the selected agricultural area.