[Accumulation and biosynthesis mechanism of volatile oils in glandular scale of Agastache rugosa].

The volatile oils are the effective components of Agastache rugosa, which are stored in the glandular scale. The leaves of pulegone-type A. rugosa were used as materials to observe the leaf morphology of A. rugosa at different growth stages, and the components of volatile oils in gland scales were detected by GC-MS. At the same time, qRT-PCR was used to determine the relative expression of key enzyme genes in the biosynthesis pathway of monoterpenes in volatile oils. The results showed that the density of A. rugosa glandular scale decreased first and then tended to be stable. With the growth of leaves, the relative content of pulegone decreased from 79.26% to 3.94%(89.97%-41.44%), while that of isomenthone increased from 2.43% to 77.87%(0.74%-51.01%), and the changes of other components were relatively insignificant. The correlation analysis between the relative content of monoterpenes and the relative expression levels of their key enzyme genes showed that there was a significant correlation between the relative content of menthone and isomenthone and the relative expression levels of pulegone reductase(PR)(r>0.6, P<0.01). To sum up, this study revealed the accumulation rules of the main components of the contents of the glandular scale of A. rugosa and the expression rules of the key enzyme genes for biosynthesis, which provided a scientific basis and data support for determining the appropriate harvesting period and quality control of the medicinal herbs. This study also initially revealed the biosynthesis mechanism of the monoterpenes mainly composed of pulegone and isomenthone in A. rugosa, laying a foundation for further research on the molecular mechanism of synthesis and accumulation of monoterpenes in A. rugosa.

Comparative Morphology of Island and Inland Agastache rugosa and Their Gastroprotective Effects in EtOH/HCl-Induced Gastric Mucosal Gastritis.

Agastache rugosa Kuntze (Lamiaceae; Labiatae), a medicinal and functional herb used to treat gastrointestinal diseases, grows well both on islands and inland areas in South Korea. Thus, we aimed to reveal the morphological and micromorphological differences between A. rugosa grown on island and inland areas and their pharmacological effects on gastritis in an animal model by combining morphological and mass spectrophotometric analyses. Morphological analysis showed that island A. rugosa had slightly smaller plants and leaves than inland plants; however, the density of all types of trichomes on the leaves, petioles, and stems of island A. rugosa was significantly higher than that of inland plants. The essential oil component analysis revealed that pulegone levels were substantially higher in island A. rugosa than in inland A. rugosa. Despite the differences between island and inland A. rugosa, treatment with both island and inland A. rugosa reduced gastric damages by more than 40% compared to the gastritis induction group. In addition, expression of inflammatory protein was reduced by about 30% by treatment of island and inland A. rugosa. The present study demonstrates quantitative differences in morphology and volatile components between island and inland plants; significant differences were not observed between the gastritis-inhibitory effects of island and inland A. rugosa, and the efficacy of island A. rugosa was found to be similar to that of A. rugosa grown in inland areas.

Development of simultaneous quantitative analytical method for three active components of Korean mint (Agastache rugosa (Fisch. & C.A.Mey.) Kuntze) extract in human plasma using ultra-high-performance liquid chromatography-tandem mass spectrometry.

Agastache rugosa contains phenolic compounds and flavonoids, and has been extensively used as a traditional herbal medicine. The major components in Agastache rugosa extract (ARE) are rosmarinic acid, tilianin, and acacetin, for which several analytical techniques have been reported. However, these substances have yet to be simultaneously quantified in human plasma. In this study, we aimed to simultaneously determine the three active components of ARE in human plasma by developing a reliable quantitative analytical method using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Chromatographic separation of the plasma samples was achieved using an ACQUITY UPLC® BEH C18 column with a gradient mobile phase of water and acetonitrile containing 0.1 % formic acid. Mass spectrometric detection was performed using a triple quadrupole tandem mass spectrometer in negative electrospray ionization (ESI-) and multiple reaction monitoring (MRM) modes. The developed quantitative method was validated for the three active components. All three analytes exhibited a linear response over the ranges of 0.5-50 ng/mL for rosmarinic acid, 0.1-20 ng/mL for acacetin, and 0.5-20 ng/mL for tilianin with a weighting factor of 1/x (where x is the concentration). At three quality control (QC) concentration levels (low, medium, and high), including the lower limit of quantitation (LLOQ), acceptable accuracy (±15 %) was achieved in the intra- and interday validations. The concentration of rosmarinic acid was highest in plasma. Tilianin and acacetin appeared and were eliminated earlier in the plasma than rosmarinic acid. This study provides a successfully validated method that can be used in further clinical applications of Agastache rugosa extracts.

Bioavailability of Korean mint (Agastache rugosa) polyphenols in humans and a Caco-2 cell model: a preliminary study exploring the efficacy.

Agastache rugosa, commonly known as Korean mint (KM), is a medicinal plant renowned for its potential health-promoting properties. However, the lack of bioavailability studies has hindered the acquisition of conclusive evidence. In this study, we investigated the bioavailability of six key polyphenols present in KM, including rosmarinic acid (RA), acacetin (AC), and four glycosides of AC. Utilizing UPLC-MS/MS, we analyzed their presence in human plasma and Caco-2 monolayers grown in permeable filter supports. Following single ingestion, we were able to detect RA, AC, and tilianin (TA) in the plasma. Consistent results were obtained for AC and TA but no transport was found for RA in a highly tight Caco-2 cell monolayer, indicating transport through the intercellular space for RA and transepithelial transport for AC and TA. Other AC glucosides with acetyl and/or malonyl groups were rarely found in the plasma. Interestingly, AC glucosides with only an acetyl group appeared at the basolateral side in Caco-2 monolayers, suggesting exclusive hydrolysis of malonyl glucosides in the colon. These findings highlight the high potential of RA, AC, and TA as bioactive compounds that may confer health benefits.

Essential Oil Composition and Enantioselective Profile of Agastache urticifolia (Lamiaceae) and Monardella odoratissima (Lamiaceae) from Utah.

Two species within the Lamiaceae (mint) family, Agastache urticifolia and Monardella odoratissima, are aromatic plants that are native to the Intermountain Region (USA). Essential oil produced through steam distillation was examined to establish the essential oil yield and both the achiral and chiral aromatic profiles of both plant species. The resulting essential oils were analyzed by GC/MS, GC/FID, and MRR (molecular rotational resonance). For A. urticifolia and M. odoratissima, achiral essential oil profiles were largely composed of limonene (71.0%, 27.7%), trans-ß-ocimene (3.6%, 6.9%), and pulegone (15.9%, 4.3%), respectively. Between the two species, eight chiral pairs were analyzed and, interestingly, the dominant enantiomer (calculated as ee%) of limonene and pulegone switched between the two species. Where enantiopure standards were not commercially available, MRR was used as a reliable analytical technique for chiral analysis. This study verifies the achiral profile for A. urticifolia and, for the first time to the authors' knowledge, establishes the achiral profile for M. odoratissima and chiral profile for both species. Additionally, this study confirms the utility and practicality of using MRR for determining chiral profiles in essential oils.

Bridging the Chemical Profile and Biological Activities of a New Variety of Agastache foeniculum (Pursh) Kuntze Extracts and Essential Oil.

This study investigated the phytochemical content of alcoholic extracts and essential oil of a new variety of medicinal plants, Agastache foeniculum (Pursh), which Kuntze adapted for cultivation in Romania, namely "Aromat de Buzau". The essential oil was investigated by GC-MS, while the identification and quantification of various compounds from alcoholic extracts were performed by HPLC-DAD. The total phenol and flavonoid contents of the extracts were evaluated by using standard phytochemical methods. The antioxidant activities of ethanol, methanol extracts, and essential oil of the plant were also assessed against 2,2'-diphenyl-1-picrylhydrazyl (DPPH•), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS•+), and by ferric reducing power (FRAP) using spectroscopic methods. Cyclic voltammetry was used to evaluate the antioxidant capacity of the essential oil. The concentrations of phenolic compounds were higher in methanolic extract compared to ethanolic extract. A significant correlation was found between total phenol and total flavonoid contents (r = 0.9087). Significant high correlations were also found between the total phenolic compounds and the antioxidant activities of the extracts (r ≥ 0.8600, p < 0.05). In addition, the extracts and essential oil showed good antioxidant and xanthine oxidase inhibitory activities. Estragole was detected as the major constituent of the essential oil (94.89%). The cytotoxic activity of the essential oil was evaluated by the MTT assay. At lower concentrations (1 µg/mL) high cytotoxicity against MCF-7 breast cancer cells was observed but not on the non-tumoral dermal fibroblasts (HDF) which indicated selectivity for cancer cells and suggests the presence of biologically active components that contribute to the observed high cytotoxic effect. Findings from the present study offer new perspectives on the use of A. foeniculum as a potential source of bioactive compounds and a good candidate for pharmaceutical plant-based products.

Chemical Diversity of Essential Oils from Korean Native Populations of Agastache rugosa (Korean Mint).

Agastache rugosa (baechohyang) is one of the most important aromatic plants native to the Republic of Korea. A. rugosa fragrance has been used to prepare incense since the Goryeo Dynasty in Korea. The present study aimed to explore the variation in the composition of essential oils from A. rugosa among native populations in Korea. The seeds of A. rugosa were collected from 90 different sites in Korea and seedlings were raised in the nursery. Essential oils were extracted from these populations by the steam distillation extraction method and their chemical compositions were analyzed by GC-MS. The yield of essential oils of A. rugosa ranged between 0.11% and 0.86%. A total of 204 components were identified from 90 populations of A. rugosa. Out of 204 components, 32 components were common in more than 40 individuals of A. rugosa and these 32 components were selected for principal component analysis (PCA). On the basis of the essential oil compositions, six chemotypes-estragole, pulegone, methyl eugenol, menthone, isopulegone, and nepetalactone-were distinguished according to their major components. As a result of the cluster analysis, 90 individuals of A. rugosa could be classified into three groups: estragole, methyl eugenol, and pulegone. A. rugosa exhibited significant chemical diversity among the individuals. The distribution of chemotypes is associated with the collection of seeds, suggesting that genetic diversity may influence the variations in the chemical compositions and concentrations within the species. This chemical diversity serves as the background to select cultivars for the cultivation and industrial applications of A. rugosa cultivars with high essential oil yield and concentration of its chemical components.

Metabolites identification for major active components of Agastache rugosa in rat by UPLC-Orbitap-MS: Comparison of the difference between metabolism as a single component and as a component in a multi-component extract.

Agastache rugosa (fisch. & C.A. Mey.) Kuntze (A. rugosa) is used in traditional medicine in Korea since it has variety of medicinal activities, such as antioxidant, anti-inflammatory, anti-photoaging. Acacetin, tilianin, and rosmarinic acid are the active components of A. rugosa but their metabolites have not yet been fully identified. The purpose of this study was to identify the metabolites of A. rugosa after oral administration in Sprague-Dawley rats. For this study, active components (acacetin, tilianin, rosmarinic acid) and A. rugosa extract were dissolved in 0.5% carboxymethyl cellulose sodium solution respectively and treated by oral gavage at a dose of 50 mg/kg (for single compounds) and 200 mg/kg (for A. rugosa extract). For metabolite identification, plasma, urine, and fecal samples were collected after oral administration and analyzed using liquid chromatography coupled with Orbitrap mass spectrometry (UPLC-Orbitrap-MS) for data acquisition and metabolite identification. Metabolite identification was performed by considering the mass difference of the metabolites from the parent compounds and using their exact m/z and MS/MS fragments. The main biotransformation of the major components of A. rugosa was hydrolysis to acacetin, followed by demethylation, methylation, and conjugation. That of rosmarinic acid is methylated and conjugated. There were differences in metabolism between the treatment of single active components and extract; some sulfate-conjugated metabolites or metabolic intermediates were only detected in the treatment of single active components. The reason for this is thought to be the low content of the active components in the extract, which react competitively with the components present in the extract in the metabolic process. This study provides valuable evidence for a comprehensive understanding of the metabolism of A. rugosa.

Fístula traumática de líquido cefalorraquídeo tras realización de test PCR mediante hisopo nasal para el diagnóstico de COVID-19. Revisión sistemática / Traumatic cerebrospinal fluid leak after performing PCR test using a nasal swab for the detection of COVID-19 disease. A Systematic review

Introducción y objetivo: Las fístulas de líquido cefalorraquídeo (LCR) pueden producirse tras un traumatismo, esto conlleva una disrupción entre la aracnoides y la duramadre, frecuentemente asociado a un defecto óseo. La epidemia mundial producida por la COVID-19 ha generado la necesidad de disponer de test rápidos para la detección del virus en mucosa nasal y orofaríngea. Los hisopos nasales (HN) han demostrado ser útiles a la hora de recoger muestras nasofaríngeas y por lo tanto se ha generalizado su uso. Este método diagnostico se considera seguro, pero existen una serie de posibles complicaciones entre las que se encuentra una de las más temidas; la fístula de LCR. El objetivo de este artículo es realizar una revisión bibliográfica exhaustiva de artículos disponibles que describan esta complicación, investigando los factores predisponentes y a su vez describir una técnica segura para evitarla.Método: Se realizaron búsquedas en las bases de datos de PubMed, Web of Science y Scopus de acuerdo con las pautas de PRISMA desde marzo de 2020 hasta noviembre de 2021. Se revisaron los estudios que informaron datos clínicos de pacientes con fistulas de LCR tras ser sometidos a frotis nasales mediante hisopos. Nos centramos en los síntomas de alarma presentados, las estrategias diagnosticas y el manejo terapéutico. Resultados: Hasta la fecha se han reportado once casos publicados de pacientes con diagnostico de fistula de LCR segundaria a la realización de test PCR mediante HN. En esta revisión sistemática se incluyen estos artículos. (AU)

Introduction and objective: Cerebrospinal fluid leaks (CSF) can occur after trauma, this leads to a disruption between the arachnoid and the dura, frequently associated with a bone defect. The global epidemic produced by COVID-19 has generated the need for rapid tests to detect the virus in the nasal and oropharyngeal mucosa. Nasal swabs (NS) have proven to be useful in collecting nasopharyngeal specimens and therefore their use has become widespread. This diagnostic method is considered safe, but there are a number of possible complications, including one of the most feared; CSF leak. The objective of this article is to carry out an exhaustive bibliographic review of available articles that describe this compli-cation, investigating the predisposing factors and describe a safe technique to avoid it. Method: PubMed, Web of Science and Scopus databases were searched according to PRISMA guidelines, from March 2020 to November 2021. Studies reporting clinical data of patients with CSF leak after being subjected to NS were reviewed. We focus on the alarm symptoms presented, diagnostic strategies and therapeutic management. Results: To date, eleven published cases have been reported of patients with a diagnosis of CSF leaks caused by performig a PCR test using a nasal swab. All the articles were included in this systematic review. Each article described this complication in one patient, so we have a total of eleven patients. The average age at diagnosis was 45 years, with 8 women and 3 men. The cribriform plate is the most frequently affected anatomical location. In five patients, 45,5%, the preexistance of malformation at the level of the skull base was known, which corresponds to a risk factor when suffering a CSF leaks after NS. (AU)

Fístula de líquido cefalorraquídeo traumática tras realización de test PCR mediante hisopo nasal para la detección de COVID-19. Descripción de un caso / Traumatic cerebrospinal fluid leak after performing PCR test using a nasal swab for the detection of COVID-19 disease. A case report

Introducción y objetivo: Las fístulas de líquido cefalorraquídeo (LCR) pueden producirse tras un traumatismo, esto conlleva una disrupción entre la aracnoides y la duramadre, frecuentemente asociado a un defecto óseo. La epidemia mundial producida por la COVID-19 ha generado la necesidad de disponer de test rápidos para la detección del virus en mucosa nasal y orofaríngea. Los hisopos nasales (HN) han demostrado ser útiles a la hora de recoger muestras nasofaríngeas y por lo tanto se ha generalizado su uso. El objetivo de este artículo recae en describir una potencial complicación del test PCR mediante HN, como es la fístula de LCR, mediante el reporte de un caso clínico. Método: Se expone el caso de una paciente que sufre una fístula de LCR tras realización de test PCR mediante HN, se explica el diagnostico y manejo detallando las pruebas complementarias y el tratamiento final. Discusión: La fístula de LCR es una complicación poco frecuente de los test con HN. A pesar de esto, existen y hay que pensar en ella ante una rinorrea unilateral persistente tras realizar este test. En la actualidad tan sólo hay escasos casos en la publicados literatura que describan esta complicación. Conclusiones: Aunque la prueba de HN para diagnostico de la COVID-19 se considera segura, en ocasiones puede conllevar complicaciones. La aparición de rinorrea clara unilateral o goteo post nasal de sabor salado o metálico tras la realización de un HN nos debe poner en alerta a la hora de diagnosticar una posible fístula de LCR. Es de suma importancia instruir adecuadamente al personal sanitario que realiza el test, indicando la dirección y orientación correcta del hisopo. Además, se debe informar al paciente sobre los síntomas y signos de alarma. En pacientes con alteraciones previas de la base del cráneo, distorsión de la anatomía nasal o cirugías previas nasosinusales puede ser recomendable utilizar en ellos otro tipo de pruebas disponibles para diagnosticar la COVID-19. (AU)

Introduction and objective: Cerebrospinal fluid leaks can occur after trauma, this leads to a disruption between the arachnoid and the dura, frequently associated with a bone defect. The global epidemic produced by COVID-19 has generated the need for rapid tests to detect the virus in the nasal and oropharyngeal mucosa. Nasal swabs (NS) have proven to be useful in collecting nasopharyngeal specimens and therefore their use has become widespread. The objective of this article is to describe a potential compli-cation of the NS PCR test, such as cerebrospinal fluid (CSF) leaks, by reporting a clinical case. Method: The case of a patient who suffers a CSF leak after performing a PCR test using a NS is presented, the diagnosis and management are explained, detailing the complementary tests and the final treatment. Discussion: CSF leaks is a rare complication of NS tests. Despite this, persistent unilateral rhinorrhea does exist and should be considered first after performing this test. Currently, there are few cases published in the literature that describe this possible complication. Conclusions: Although the NS test for the diagnosis of COVID-19 is considered safe, it can sometimes lead to complications. The appearance of unilateral clear rhinorrhea or post-nasal drip with a salty or metallic taste after performing a NS should alert us when diagnosing a possible CSF leak. It is extremely important to adequately instruct the health workers to perform the test, indicating the correct direction and orientation of the swab. In addition, the patient should be informed of the warning signs and symptoms. In patients with previous skull base alterations, distortion of the nasal anatomy or previous sinus surgeries, it may be advisable to use other types of tests available to diagnose COVID-19. (AU)

Holistic quality evaluation of commercial Agastache rugosa by multiple chromatographic and chemometric analysis.

In present study, a comprehensive strategy integrating multiple chromatographic and chemometric methods to simultaneously characterize the volatile and non-volatile components was developed for the holistic quality evaluation of commercial Agastache rugosa (AR), a common edible and medicinal herb, collected in China. The volatile components and the non-volatile components were characterized by GC-MS and UPLC-QTOF-MS/MS, respectively. And the data were analyzed either independently or integratively by multivariate statistical analysis (MVS) for the quality assessment of commercial samples. The results revealed that the commercial AR samples were different in both the composition and the content of volatile components. However, the compositions of non-volatile components in commercial AR were generally similar, whereas the contents of some components were different. All the results indicated that the holistic quality of commercial AR was inconsistent, and the commercial samples collected could be classified into two main groups, the volatile components were majorly responsible for the classification. Whether or not the holistic quality variations affect the efficacy of AR deserves further investigation.

Anti-oxidative and anti-hyperglycemic properties of Agastache foeniculum essential oil and oily fraction in hyperglycemia-stimulated and lipopolysaccharide-stimulated macrophage cells: In vitro and in silico studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperglycemia (HG) and lipopolysaccharide (LPS) often promote superoxide accumulation, which may increase oxidative stress. Reducing superoxide production in hyperglycemia and the inflammatory condition is an emerging way to reduce protein and lipid oxidation and diabetes complication. AIM OF STUDY: To examine the effect of Agastache foeniculum essential oil (AFEO) and oil fraction (AFoil) on HG- and LPS-stimulated oxidative stress, the pathogenicity of AFEO and AFoil on oxidative stress was assessed. METHODS: The stimulatory effects of AFEO and AFoil on the activity and expression of NADH oxide (NOX), catalase (CAT), superoxide dismutase (SOD), and the expression of nuclear respiratory factor 2 (NRF2) and nuclear factor-kappa B (NF-kB) in the stimulated macrophage cell line, J774.A1, was studied. The interaction patterns of AFEO and AFoil components with NOX, SOD, CAT, NRF2, and NF-kB proteins were also deduced using molecular docking. RESULTS: Estragole was the main ingredient in AFEO (97%). Linolenic acid (32.10%), estragole (16.22%), palmitic acid (12.62%), linoleic acid (12.04%), and oleic acid (8.73%) were the major chemical components of the AFoil. NOX activation was stimulated in macrophage cells by HG and LPS. At 20 µg/mL, AFEO and AFoil decreased NOX activity while increased SOD and CAT activities in stimulated macrophages. AFoil with estragole and omega-3 fatty acids was better than AFEO with estragole in anti-hyperglycemic and anti-oxidative activity. According to molecular docking research, estragole, linoleic acid, and linolenic acid bind to different hydrophobic pockets of NOX, SOD, CAT, NFR2, and NF-kB using hydrogen bonds, van der Waals bonds, pi-alkyl, and pi-anion interactions, with different binding energies. CONCLUSION: AFEO and AFoil showed antioxidant and anti-diabetic activity. The mechanisms in lowering oxidative stress markers depended on down-regulating superoxide-producing enzymes and up-regulating superoxide-removing enzymes at gene and protein levels. The AFoil emulsion can be used to reduce the detrimental impacts of hyperglycemia and oxidative stress.

Herbaceous perennial ornamental plants can support complex pollinator communities.

Human-designed landscapes can host diverse pollinator communities, and the availability of floral resources is central to supporting insect biodiversity in highly modified environments. However, some urban landscapes have relatively few pollinator-attractive plant species and management in urban environments rarely considers the function of these plants in generating and supporting a stable ecological community. Evaluations of 25 cultivars within five commercially popular herbaceous perennial ornamental plant genera (Agastache, Echinacea, Nepeta, Rudbeckia, and Salvia) revealed variation in the total and proportional abundance of visitors attracted. These varieties supported multiple pollinator functional groups, however bees were the primary visitors to in this system. Cultivars were assessed according to their function within a plant-pollinator network. Comparisons of artificial networks created with the six most attractive and six least attractive cultivars demonstrated that a planting scheme using the most attractive cultivars would attract nearly four times as many bee species, including several specialists and rare species. Plant diversity in the landscape was correlated with abundance and diversity of pollinator visitors, demonstrating that community context shapes a plant's relative attractiveness to pollinators. We conclude that herbaceous perennial cultivars can support an abundance and diversity of pollinator visitors, however, planting schemes should take into consideration the effects of cultivar, landscape plant diversity, floral phenology, floral area, and contribution to a stable ecological community.

A Systematic Approach to Agastache mexicana Research: Biology, Agronomy, Phytochemistry, and Bioactivity.

Mexico is the center of origin of the species popularly known as toronjil or lemon balm (Agastache mexicana Linton & Epling). Two subspecies have been identified and are commonly called purple or red (Agastache mexicana Linton & Epling subspecies. mexicana) and white (Agastache mexicana subspecies xolocotziana Bye, E.L. Linares & Ramamoorthy). Plants from these subspecies differ in the size and form of inflorescence and leaves. They also possess differences in their chemical compositions, including volatile compounds. Traditional Mexican medicine employs both subspecies. A. mexicana exhibits a broad range of pharmacological properties, such as anti-inflammatory, anxiolytic, and antioxidant. A systematic vision of these plant's properties is discussed in this review, exposing its significant potential as a source of valuable bioactive compounds. Furthermore, this review provides an understanding of the elements that make up the species' holistic system to benefit from lemon balm sustainably.

Limonene from Agastache mexicana essential oil produces antinociceptive effects, gastrointestinal protection and improves experimental ulcerative colitis.

ETHNOPHARMACOLOGY RELEVANCE: Agastache mexicana is a popular plant of great demand in folk medicine, essentially due to its calming properties and for alleviating arthritic, muscular and abdominal pain. Despite its spectrum for pain relief, pharmacological studies of its bioactive constituents have been barely investigated. AIM OF THE STUDY: To evaluate protective properties of the A. mexicana and bioactive compounds improving pathological gastrointestinal conditions in rodents. MATERIAL AND METHODS: Different doses of the essential oil of A. mexicana ssp. mexicana and ssp. xolocotziana (30-562.2 mg/kg, i.p.) and individual monoterpenes (3-300 mg/kg, i.p.) were evaluated in an abdominal pain model. The most active monoterpene limonene and sulfasalazine (reference drug, 100 mg/kg, p.o.) were also evaluated in the oxazolone-induced colitis model using an oral gavage, where some inflammatory cytokines were analyzed by enzyme-linked immunosorbent assays. Finally, colonic histological assessment and gastroprotection in the absolute ethanol-induced ulcer model were explored. RESULTS: Our results demonstrated that the essential oil of both subspecies produced a significant reduction in the abdominal writhes, where monoterpenes limonene and pulegone were partially responsible bioactive metabolites. Limonene showed the major antinociceptive efficacy in the writhing test. It also significantly decreased hyperalgesia, pathological biomarkers, and colonic inflammatory cytokines in the oxazolone-induced colitis model, as well as prevention in gastric damage. CONCLUSIONS: Present results provide scientific evidence to reinforce the use of A. mexicana in the traditional medicine for gastrointestinal conditions, mainly related to pain and inflammation, demonstrating the potential of monoterpenes as natural products in the therapeutics of gastrointestinal affections such as ulcer, colitis, and abdominal pain.

Chemical Analyses and Antimicrobial Activity of Nine Kinds of Unifloral Chinese Honeys Compared to Manuka Honey (12+ and 20+).

Honey has good antimicrobial properties and can be used for medical treatment. The antimicrobial properties of unifloral honey varieties are different. In this study, we evaluated the antimicrobial and antioxidant activities of nine kinds of Chinese monofloral honeys. In addition, headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) technology was used to detect their volatile components. The relevant results are as follows: 1. The agar diffusion test showed that the diameter of inhibition zone against Staphylococcus aureus of Fennel honey (21.50 ± 0.41 mm), Agastache honey (20.74 ± 0.37 mm), and Pomegranate honey (18.16 ± 0.11 mm) was larger than that of Manuka 12+ honey (14.27 ± 0.10 mm) and Manuka 20+ honey (16.52 ± 0.12 mm). The antimicrobial activity of Chinese honey depends on hydrogen peroxide. 2. The total antioxidant capacity of Fennel honey, Agastache honey, and Pomegranate honey was higher than that of other Chinese honeys. There was a significant positive correlation between the total antioxidant capacity and the total phenol content of Chinese honey (r = 0.958). The correlation coefficient between the chroma value of Chinese honey and the total antioxidant and the diameter of inhibition zone was 0.940 and 0.746, respectively. The analyzed dark honeys had better antimicrobial and antioxidant activities. 3. There were significant differences in volatile components among Fennel honey, Agastache honey, Pomegranate honey, and Manuka honey. Hexanal-D and Heptanol were the characteristic components of Fennel honey and Pomegranate honey, respectively. Ethyl 2-methylbutyrate and 3-methylpentanoic acids were the unique compounds of Agastache honey. The flavor fingerprints of the honey samples from different plants can be successfully built using HS-GC-IMS and principal component analysis (PCA) based on their volatile compounds. Fennel honey, Agastache honey, and Pomegranate honey are Chinese honey varieties with excellent antimicrobial properties, and have the potential to be developed into medical grade honey.

Agastache rugosa ethanol extract suppresses bone loss via induction of osteoblast differentiation with alteration of gut microbiota.

PURPOSE: Osteoporosis is a metabolic skeletal disease characterized by bone loss and an increased risk of fractures. This study aimed to investigate the therapeutic effect of Agastache rugosa on postmenopausal osteoporosis and elucidate its mechanisms in modulating the bone status. METHODS AND RESULTS: In the osteoblast differentiation process with MC3T3-E1 pre-osteoblasts, ethanol extract of Agastache rugosa (EEAR) and its compounds increased the expression of the proteins and genes of the osteoblast differentiation-related markers such as Runt-related transcription factor 2 (RUNX2) and ß-catenin along with the elevation of calcium deposits. An ovariectomized mouse model was utilized to determine the impact of EEAR extract on postmenopausal osteoporosis. Twelve weeks of AR treatment suppressed the loss of bone strength, which was observed through micro-computed tomography. AR elevated osteogenic markers in the bone marrow cells, and collagen type 1 alpha 1 in the distal femoral bone. The results of the 16S rRNA gene sequencing analysis of cecal gut microbiomes demonstrated that AR reversed the ovariectomy-induced changes in the gut microbiomes. CONCLUSION: Ethanol extract of Agastache rugosa has a therapeutic effect on postmenopausal osteoporosis via bone morphogenic protein, transforming growth factor ß, and Wnt signaling pathway. It also increases the diversity of gut microbiota. Therefore, these data suggest that EEAR could be a potential candidate to treat postmenopausal osteoporosis.

Anti-Inflammatory, Barrier-Protective, and Antiwrinkle Properties of Agastache rugosa Kuntze in Human Epidermal Keratinocytes.

This work aimed to assess the skin-beneficial properties of Agastache rugosa Kuntze, an herbal medication used to treat different types of disorders in traditional folk medicine. The total phenolic compounds and total antiradical, nitrite scavenging, superoxide scavenging, antielastase, and antihyaluronidase activities of a hot water extract of A. rugosa Kuntze leaves (ARE) were spectrophotometrically determined. Intracellular reactive oxygen species (ROS) was fluorometrically quantitated using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Inducible nitric oxide synthase (iNOS) and filaggrin were evaluated using Western analysis. Real-time quantitative RT-PCR was used to measure filaggrin mRNA. Caspase-14 activity was determined using a fluorogenic substrate. ARE contained the total phenolic content of 38.9 mg gallic acid equivalent/g extract and exhibited 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide radical, and nitrite scavenging activities with the SC50 values of 2.9, 1.4, and 1.7 mg/mL, respectively. ARE exerted suppressive activities on nitric oxide (NO) and ROS levels elevated by lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α) in HaCaT keratinocytes. It attenuated the LPS-stimulated expression of iNOS. ARE augmented the UV-B-reduced filaggrin expression on both protein and mRNA levels and was capable of upregulating the UV-B-reduced caspase-14 activity. ARE inhibited in vitro elastase and hyaluronidase activities associated with the wrinkling process. ARE, at the concentrations used, did not interfere with the viability of HaCaT keratinocytes. These findings preliminarily imply that the leaves of A. rugosa possess desirable cosmetic potentials, such as anti-inflammatory, barrier protective, and antiwrinkle activities, which infers their skin healing potentials.

Pharmacological Effects of Agastache rugosa against Gastritis Using a Network Pharmacology Approach.

Agastache rugosa is used as a Korean traditional medicine to treat gastric diseases. However, the active ingredients and pharmacological targets of A. rugosa are unknown. In this study, we aimed to reveal the pharmacological effects of A. rugosa on gastritis by combining a mice model and a network pharmacology method. The macrophage and gastritis-induced models were used to evaluate the pharmacological effects of A. rugosa. The results show that A. rugosa relieved mucosal damage induced by HCl/EtOH in vivo. Network analysis identified 99 components in A. rugosa; six components were selected through systematic screening, and five components were linked to 45 gastritis-related genes. The main components were acacetin and luteolin, and the identified core genes were AKT serine/threonine kinase 1 (AKT1), nuclear factor kappa B inhibitor alpha (NFKBIA), and mitogen-activated protein kinase-3 (MAPK3) etc. in this network. The network of components, target genes, protein-protein interactions, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was closely connected with chemokines and with phosphoinositide 3-kinase-Akt (PI3K/AKT), tumor-necrosis-factor alpha (TNFα), mitogen-activated protein kinase, nuclear factor kappa B, and Toll-like receptor (TLR) pathways. In conclusion, A. rugosa exerts gastro-protective effects through a multi-compound and multi-pathway regulatory network and holds potential for treating inflammatory gastric diseases.

Domestication of aromatic medicinal plants in Mexico: Agastache (Lamiaceae)-an ethnobotanical, morpho-physiological, and phytochemical analysis.

BACKGROUND: Most reports of domesticated plants that involve a domestication gradient or inter-specific hybridization in Mexico have focused on those used as food. This study provides knowledge about these processes in two aromatic medicinal plants, Agastache mexicana (Lamiaceae) and A. m. subsp. xolocotziana, widely used in Mexican traditional medicine for the treatment of gastrointestinal ailments and for their sedative effect. Different populations of A. mexicana along a gradient of domestication are found in the foothills of the Popocatepetl volcano of central Mexico, while in this same area the subsp. xolocotziana grows only in the cultivation, possibly a product of hybridization between A. mexicana and Agastache palmeri. This study links ethnobotanical, morpho-physiological, and phytochemical evidence to document the domestication of both taxa as well as elucidates the possible hybrid origin of the subsp. xolocotziana. METHOD: We analyze three groups of data derived from (1) 80 semi-structured interviews aimed at documenting the selection criteria related to the use and management of A. mexicana; (2) a cultivation experiment under homogeneous conditions, evaluating 21 floral, vegetative, and seed characters (that were important according to ethnobotanical information) in 97 plants corresponding to 13 populations of the taxa under study; and (3) the chemical profiles of the essential oils of these plants by means of a thin-layer chromatography. RESULTS: By linking the three types of evidence, two evolutionary processes are distinguished: (1) A. mexicana occurs in the encouraged-cultivated phases of the domestication gradient and (2) A. m. subsp. xolocotziana may have originated through inbreeding depression or hybridization. These two cultivated plants show a domestication syndrome based upon organoleptic differentiation due to their dissimilar phytochemical composition and gigantism in flowers, seeds, and rhizomes (the last enhancing their asexual reproductive capacity). In addition to this, A. mexicana exhibits more intense floral pigmentation and foliar gigantism while subsp. xolocotziana presents floral albinism and partial seed sterility. CONCLUSION: Two divergent evolutionary processes are reported for the domestication of A. mexicana as a result of the intensification of its use and management. The selection processes of these plants have resulted in alternation of the organoleptic properties based upon the divergence of the phytochemical composition. Also, gigantism has been selected in culturally preferred plant parts and in correlated structures. The preceding characteristics reinforce the joint use of these plants in infusion in Mexican traditionalmedicine for the treatment of gastrointestinal diseases and for their sedative effects.