Dryopteris crassirhizoma Nakai.: A review of its botany, traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics.

ETHNOPHARMACOLOGICAL RELEVANCE: The Dryopteris crassirhizoma Nakai., a commonly used herb, is known as "Guan Zhong" in China, "Oshida" in Japan and "Gwanjung" in Korea. It has long been used for parasitic infestation, hemorrhages and epidemic influenza. AIM OF THE REVIEW: The present paper aims to provide an up-to-date review at the advancements of the investigations on the traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics of D. crassirhizoma. Besides, possible trends, therapeutic potentials, and perspectives for future research of this plant are also briefly discussed. MATERIALS AND METHODS: Relevant information on traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics of D. crassirhizoma was collected through published materials and electronic databases, including the Chinese Pharmacopoeia, Flora of China, Web of Science, PubMed, Baidu Scholar, Google Scholar, and China National Knowledge Infrastructure. 109 papers included in the article and we determined that no major information was missing after many checks. All authors participated in the review process for this article and all research paper are from authoritative published materials and electronic databases. RESULTS: 130 chemical components, among which phloroglucinols are the predominant groups, have been isolated and identified from D. crassirhizoma. D. crassirhizoma with its bioactive compounds is possessed of extensive biological activities, including anti-parasite, anti-microbial, anti-viral, anti-cancer, anti-inflammatory, anti-oxidant, anti-diabetic, bone protective, immunomodulatory, anti-platelet and anti-hyperuricemia activity. Besides, D. crassirhizoma has special toxicology and pharmacokinetics characterization. CONCLUSIONS: D. crassirhizoma is a traditional Chinese medicine having a long history of application. This review mainly summarized the different chemical components extract from D. crassirhizoma and various reported pharmacological effects. Besides, the toxicology and pharmacokinetics of D. crassirhizoma also be analysed in this review. However, the chemical components of D. crassirhizoma are understudied and require further research to expand its medicinal potential, and it is urgent to design a new extraction scheme, so that the active ingredients can be obtained at a lower cost.

Simultaneous Study of Analysis of Anti-inflammatory Potential of Dryopteris ramosa (C. Hope) C. Chr. using GC-Mass and Computational Modeling on the Xylene-induced Ear Oedema in Mouse Model.

INTRODUCTION: In the present study, we aimed to investigate the extraction and identification of the potential phytochemicals from the Methanolic Extract of Dryopteris ramosa (MEDR) using GC-MS profiling for validating the traditional uses of MEDR its efficacy in inflammations by using in-vitro, in-vivo and in silico approaches in anti-inflammatory models. METHODS: GC-MS analysis confirmed the presence of a total of 59 phytochemical compounds. The human red blood cells (HRBC) membrane stabilization assay and heat-induced hemolysis method were used as in-vitro anti-inflammatory activity of the extract. The in-vivo analysis was carried out through the Xylene-induced mice ear oedema method. It was found that MEDR at a concentration of 20 µg, 30 µg, and 40 µg showed 35.45%, 36.01%, and 36.33% protection to HRBC in a hypotonic solution, respectively. At the same time, standard Diclofenac at 30 µg showed 45.31% protection of HRBC in a hypotonic solution. RESULTS: The extract showed inhibition of 25.32%, 26.53%, and 33.31% cell membrane lysis at heating at 20 µg, 30 µg, and 40 µg, respectively. In comparison, standard Diclofenac at 30 µg showed 50.49% inhibition of denaturation to heat. Methanolic extract of the plant exhibited momentous inhibition in xylene-induced ear oedema in mice treated with 30 µg extract were 47.2%, 63.4%, and 78.8%, while inhibition in mice ear oedema treated with 60 µg extract was 34.7%, 43.05%, 63.21% and reduction in ear thickness of standard drug were 57.3%, 59.54%, 60.42% recorded at the duration of 1, 4 and 24 hours of inflammation. Molecular docking and simulations were performed to validate the anti-inflammatory role of the phytochemicals that revealed five potential phytochemicals i.e. Stigmasterol,22,23dihydro, Heptadecane,8methyl, Pimaricacid, Germacrene and 1,3Cyclohexadiene,_5(1,5dimethyl4hexenyl)-2methyl which revealed potential or significant inhibitory effects on cyclooxygenase-2 (COX-2), tumour necrosis factor (TNF-α), and interleukin (IL-6) in the docking analysis. CONCLUSION: The outcome of the study signifies that MEDR can offer a new prospect in the discovery of a harmonizing and alternative therapy for inflammatory disease conditions.

Dryoptkirbioside, A New Fructofuranoside Glycerol, and Other Constituents from Dryopteris kirbi Hook et Grav Rhizomes.

A new fructofuranoside glycerol, dryoptkirbioside (1), along with thirteen known compounds (2-14), was isolated from the MeOH extract of Dryopteris kirbi rhizomes by silica gel column chromatography, Sephadex LH-20 column chromatography, and semipreparative HPLC. The structure of the new compound was determined by analyses of its spectroscopic data including nuclear magnetic resonance (NMR), and high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) and chemical conversions. The hexane-soluble portion and the EAFA fraction showed strong activities against lung (A549), breast (MCF-7), and cervical (HeLa) human cancer cell lines (IC50 values ranging from 4.0 to 8.8 µg/mL). Aspidinol P (5) and aspidinol B (6) exhibited moderate to low cytotoxicity on the three cell lines (IC50 values ranging from 20.4 to 58.7 µM). The MeOH extract and hexane-soluble portion had excellent activities against Staphylococcus aureus and Bacillus subtilis (MICs 11.7 and 23.4 µg/mL), whereas the AcOEt- and BuOH-soluble portions were significantly active on S. aureus (MICs 46.9 and 93.8 µg/mL). The main fractions EAFB , EAFC and nBFB displayed excellent activity against S. aureus (MICs 11.7 and 23.4 µg/mL). Aspidinol B (6) had significant activity, while aspidinol P (5) was moderately active against S. aureus and B. subtilis (MICs 42.0 and 89.5 µM).

New tocopherol and acylphloroglucinol derivatives from Dryopteris crassirhizoma and their antimicrobial activities.

Nine previously undescribed compounds including six tocopherol derivatives (1-6) and three acylphloroglucinol derivatives (7-9) were isolated and characterized from the plants of Dryopteris crassirhizoma. Their structures with absolute configurations were determined by extensive spectroscopic analyses, including IR, HRESIMS, NMR, and calculated electronic circular dichroism (ECD). Compounds 1 and 2 are the first tocopheroid derivatives possessing unique 2,5-dimethylcyclopent-4-ene-1,3-dione carbon skeleton, and compounds 3-6 were new 5a-norcyclopentenones having a spirofused bicyclic carbon skeleton. The biosynthetic pathway of compounds 1-6 was postulated. When combined with fluconazole (FLC), compound 3 showed significant antifungal activity against standard Candida albicans with MIC50 value of 1.19 µg/mL (FLC: 3.41 µg/mL). Furthermore, the anti-plant pathogenic fungi and bacterial activities have been evaluated in vitro, compounds 5 and 8 showed anti-Verticillium dahlia and Sclerotinia sclerotiorum with MIC value of 50 µg/mL, respectively. Compounds 1 and 5 exhibited moderate antibacterial activities against Micrococcus luteus with MIC value of 50 µg/mL, respectively.

Antimicrobial Acylphloroglucinol Meroterpenoids and Acylphloroglucinols from Dryopteris crassirhizoma.

Ten novel meroterpenoids, dryoptins/11″-epi-dryoptins A~E (1: ~10: ) with an unprecedented skeleton consisting of dimeric or trimeric acylphloroglucinols and dehydrotheonelline, two undescribed acylphloroglucinol-nerolidol meroterpenoids (11: ~12: ), and ten known acylphloroglucinol derivatives (13: ~22: ), were isolated from D. crassirhizoma. The novel structures including absolute configurations were established by comprehensive spectroscopic analyses and quantum chemical electronic circular dichroism (ECD) calculations. A biosynthetic pathway of 1: ~10: was assumed. The trimeric acylphloroglucinol meroterpenoids 7: /8: showed significant antifungal activity against standard Candida albicans with a MIC50 value of 1.61 µg/mL [fluconazole (FLC): 3.41 µg/mL], and when combined with FLC, the principal components 20: and 21: exhibited strong antifungal activities against FLC-resistant C. albicans with MIC50 values of 8.39 and 7.16 µg/mL (FLC: > 100 µg/mL), respectively. Moreover, compounds 2, 5: /6, 18, 19: , and 21: exhibited inhibitory effects against several pathogenic fungi and bacteria, with MIC50 values of 6.25 ~ 50 µg/mL.

Evaluation of Safety of Stewart's Wood Fern (Dryopteris stewartii) and Its Anti-Hyperglycemic Potential in Alloxan-Induced Diabetic Mice.

Diabetes has become a critical challenge to the global health concerns. Cytotoxicity and development of resistance against available drugs for management of diabetes have shifted the focus of global scientific researchers from synthetic to herbal medications. Therefore, the current study was conducted to investigate the possible anti-hyperglycemic potential of Dryopteris stewartii using Swiss albino mice. To evaluate any possible toxic effect of the plant, acute oral toxicity test was performed while the anti-diabetic effects of aqueous and ethanol extracts at 500 mg/kg, positive, negative and normal control were assessed simultaneously. The anti-diabetic study revealed that aqueous extract has higher anti-diabetic potential than ethanol extract while lowered blood glucose level at second week reaching 150 mg/dL, exerting stronger anti-diabetic effects, compared to ethanol extract (190 mg/dL). Oral glucose tolerance findings revealed that aqueous extract decreased blood glucose level by -0.41-fold, compared to ethanol extract showing a decrease by only -0.29-folds. The histopathological evaluation of liver and pancreas of all groups revealed normal cell architecture with no morphological abnormalities. These results suggested the possible use of D. stewartii as anti-diabetic herbal drug in near future. However, these recommendations are conditioned by deep mechanistic studies.

Comparison of Constituents and Antioxidant Activity of Above-Ground and Underground Parts of Dryopteris crassirhizoma Nakai Based on HS-SPME-GC-MS and UPLC/Q-TOF-MS.

Dryopteris crassirhizoma Nakai is a Chinese traditional medicinal fern plant for heat-clearing and detoxifying, promoting blood circulation and dissipating blood stasis. Previous researches showed that many factors could influence the components of medicinal plants, and the plant part is one of the main factors. So far, only the underground part of D. crassirhizoma, called "Mianma Guanzhong", has been widely sold in the market. However, the above-ground part was usually at low utilization, resulting in a waste of medicinal resources. In order to further develop and utilize the medicinal resources of D. crassirhizoma, the constituents, total flavonoid contents and antioxidant activity of the above-ground and underground parts of D. crassirhizoma were tentatively analyzed and compared based on HS-SPME-GC-MS and UPLC/Q-TOF-MS. The results showed that (1) the volatile components were mainly focused in the above-ground part of D. crassirhizoma, including 3-carene, isoledene, ionene, 4-amino-1-naphthol and furfural. (2) Nonvolatile components of the underground part of D. crassirhizoma contained phenolic acid, flavonoids, phloroglucinol and less fatty acid. (3) The common compounds of the above-ground and underground parts of D. crassirhizoma were phenolic acid and flavaspidic acid AB. (4) Antioxidant activity of the underground part was stronger than that of the above-ground part of D. crassirhizoma. In conclusion, both the above-ground and underground parts of D. crassirhizoma are important medicinal resources worthy of further development.

Overexpression of DfRaf from Fragrant Woodfern (Dryopteris fragrans) Enhances High-Temperature Tolerance in Tobacco (Nicotiana tabacum).

Heat stress seriously affects medicinal herbs' growth and yield. Rubisco accumulation factor (Raf) is a key mediator regulating the activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), which plays important roles in carbon assimilation and the Calvin cycle in plants. Raf has been studied in many plants, but has rarely been studied in the important medicinal plant fragrant woodfern (Dryopteris fragrans). The aim of this study was to analyze the effects of Raf on carbohydrate metabolism and the response to heat stress in medicinal plants. In this study, high temperature treatment upregulated the expression of DfRaf, which was significantly higher than that of phosphoribokinase (DfPRK), Rubisco small subunits (DfRbcS), Rubisco large subunits (DfRbcL) and Rubisco activase (DfRCA). The subcellular localization showed that the DfRaf proteins were primarily located in the nucleus; DfPRK, DfRbcS, DfRbcL and DfRCA proteins were primarily located in the chloroplast. We found that overexpression of DfRaf led to increased activity of Rubisco, RCA and PRK under high-temperature stress. The H2O2, O2- and MDA content of the DfRaf-OV-L2 and DfRaf-OV-L6 transgenic lines were significantly lower than those of WT and VC plants under high-temperature stress. The photosynthetic pigments, proline, soluble sugar content and ROS-scavenging ability of the DfRaf-OV-L2 and DfRaf-OV-L6 transgenic lines were higher than those of WT and VC plants under high-temperature stress. The results showed that overexpression of the DfRaf gene increased the Rubisco activity, which enhanced the high-temperature tolerance of plants.

Integrated mRNA and miRNA Transcriptome Analysis Suggests a Regulatory Network for UV-B-Controlled Terpenoid Synthesis in Fragrant Woodfern (Dryopteris fragrans).

Fragrant woodfern (Dryopteris fragrans) is a medicinal plant rich in terpenoids. Ultraviolet-B (UV-B) light could increase concentration of terpenoids. The aim of this study was to analyze how UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern. In this study, compared with the control group, the content of the terpenes was significantly higher in fragrant woodfern leaves under UV-B treatment for 4 days (d). In order to identify how UV-B regulates the terpenoid metabolic mechanism in fragrant woodfern, we examined the mRNAs and small RNAs in fragrant woodfern leaves under UV-B treatment. mRNA and miRNA-seq identified 4533 DEGs and 17 DEMs in the control group compared with fragrant woodfern leaves under UV-B treatment for 4 d. mRNA-miRNA analysis identified miRNA target gene pairs consisting of 8 DEMs and 115 miRNAs. The target genes were subjected to GO and KEGG analyses. The results showed that the target genes were mainly enriched in diterpene biosynthesis, terpenoid backbone biosynthesis, plant hormone signal transduction, MEP pathway and MVA pathway, in which miR156 and miR160 regulate these pathways by targeting DfSPL and DfARF, respectively. The mRNA and miRNA datasets identified a subset of candidate genes. It provides the theoretical basis that UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern.

[A new phloroglucinol from Dryopteris fragrans and its antibacterial activity in vitro].

A new phloroglucinol was isolated from 50% ethanol extract of Dryopteris fragrans by silica gel column chromatography, Sephadex LH-20 gel column chromatography, thin-layer chromatography(TLC), and preparative liquid column chromatography. On the basis of MS, ~1H-NMR, ~(13)C-NMR, and reference materials, compound 1 was identified as 2,5-cyclohexadien-1-one, 2-{[2,6-dihydroxy-4-methoxy-3-methyl-5-(1-isobutyl)phenyl]methyl}-3,5-dihydroxy-4,4-dimethyl-6-(1-oxobutyl)(1), and named disaspidin BB. Compound 1 was evaluated for its antibacterial activity. The experimental results showed that compared with the commonly used topical antibiotics erythromycin or mupirocin, disaspidin BB exhibited significant antibacterial activities against Staphylococcus epidermidis(SEP), S. haemolyticus(SHA), and methicillin-resistant S. aureus(MRSA)(P<0.05). Additionally, disaspidin BB was sensitive to ceftazidime-resistant SEP1-SEP4, SHA5-SHA7, MRSA8, and MRSA9. The MIC values of disaspidin BB against SEP and SHA were 1.67-2.71 µg·mL~(-1) and 10.00-33.33 µg·mL~(-1) respectively. Disaspidin BB has good antibacterial activities and deserves development as a new anti-infective drug for external use.

A new phloroglucinol from Dryopteris fragrans and its antibacterial activity in vitro / 中国中药杂志

A new phloroglucinol was isolated from 50% ethanol extract of Dryopteris fragrans by silica gel column chromatography, Sephadex LH-20 gel column chromatography, thin-layer chromatography(TLC), and preparative liquid column chromatography. On the basis of MS, ~1H-NMR, ~(13)C-NMR, and reference materials, compound 1 was identified as 2,5-cyclohexadien-1-one, 2-{[2,6-dihydroxy-4-methoxy-3-methyl-5-(1-isobutyl)phenyl]methyl}-3,5-dihydroxy-4,4-dimethyl-6-(1-oxobutyl)(1), and named disaspidin BB. Compound 1 was evaluated for its antibacterial activity. The experimental results showed that compared with the commonly used topical antibiotics erythromycin or mupirocin, disaspidin BB exhibited significant antibacterial activities against Staphylococcus epidermidis(SEP), S. haemolyticus(SHA), and methicillin-resistant S. aureus(MRSA)(P<0.05). Additionally, disaspidin BB was sensitive to ceftazidime-resistant SEP1-SEP4, SHA5-SHA7, MRSA8, and MRSA9. The MIC values of disaspidin BB against SEP and SHA were 1.67-2.71 μg·mL~(-1) and 10.00-33.33 μg·mL~(-1) respectively. Disaspidin BB has good antibacterial activities and deserves development as a new anti-infective drug for external use.

In vivo acute toxicity, laxative and antiulcer effect of the extract of Dryopteris Ramose.

Dryopteris ramosa (D. ramosa) is one of the most traded medicinally important plants of Himalayan region. Apart from other uses, D. ramosa is traditionally also used to treat gastric ulcers and as a laxative. The present study was designed to investigate the role of methanolic crude extract of Dryopteris Ramosa (MEDR) in acute toxicity, against loperamide induced constipated mice model, antiulcer effect of methanolic extract of D. Ramosa and cholinomimetic like effect of methanolic extract of D. Ramosa. The crude extract was investigated for the presence of active compounds (secondary metabolites) such as alkaloids, flavonoids, carbohydrates, glycosides, terpenoids, phenolic compounds, saponins, and tannins following the standard methods. The antiulcer effect was investigated in mice using the ethanol induced ulcer model at various doses i.e. 50 mg/kg, 100 mg/kg and 200 mg/kg doses. Constipation was induced in the mice via loperamide (3mg/kg body weight). The control group received normal saline. Different doses of plant extracts (50, 100, 150 and 200 mg/kg body weight/day) were administered for 7 days. Various parameters like feeding characteristics, gastrointestinal transit ratio, body weight, fecal properties and the possible mechanism of action of D. Ramosa on intestinal motility were monitored. Various Phytochemicals like saponins, glycosides, flavonoids, tannins, phenols, carbohydrate, alkaloids and triterpenes were found in D. Ramosa. The acute toxicity study showed that MEDR was associated with no mortality except mild and moderate sedation at the highest tested doses (1500 and 2000 mg/kg). MEDR also showed significant antiulcer activity against ethanol-induced ulcerogenesis. The extract enhanced the intestinal motility, normalized the body weight of constipated mice and increased the fecal volume which are indications of laxative property of the herb. The 200 mg/kg body weight dose of the extract was found effective. The presence of various Phytochemicals such as flavonoids, glycosides and tannins might be responsible for the antiulcer activity of D. Ramosa. This study provides the scientific background for the folkloric use of D. Ramosa as antiulcer agent. The laxative action of the extract compares positively with Duphalac, (standard laxative drug). These findings have therefore evidence scientific background to the folkloric use of the herb as a laxative agent.

Anti-diabetogenic and in vivo antioxidant activity of ethanol extract of Dryopteris dilatata in alloxan-induced male Wistar rats.

AIMS: Oxido-inflammatory stress has been implicated as the main targets in alleviating diabetic complications induced by hyperglycaemia. Dryopteris dilatata: a bioactive plant serves great medicinal benefits in ethnopharmacology to ameliorate pathological conditions. This study investigated the protective effects of ethanol extract of Dryopteris dilatata (EEDD) in alloxan-induced diabetic rats through mechanism involving inhibition of oxidative stress and liver and kidney inflammatory markers. METHODOLOGY: Male Wistar rats were made diabetic via alloxan monohydrate (100 mg/kg) administration intraperitoneally. Diabetic rats were post-treated with EEDD (800 mg/kg) and Metformin (50 mg/kg) orally for two weeks. Fasting blood sugar (FBS), body and organ weight change, markers of oxidative stress, liver and kidney inflammation were evaluated. RESULTS: Our results revealed that EEDD significantly reduced alloxan-induced hyperglycaemia in the diabetic rats after 5, 10 and 15 days of treatment. Markers of oxidative injury were also significantly ameliorated in the pancreas, liver and kidney of the diabetic rats following treatment with EEDD. However, liver and kidney injury markers were significantly attenuated with marked decreased organ weight in the diabetic rats after treatment with EEDD. CONCLUSION: Here in, we found that Dryopteris dilatata could be used as nutraceuticals in the prevention and treatment of diabetes and its related complications through positively modulating oxidative stress and liver and kidney inflammatory markers.

Phytochemical, antimicrobial, antioxidant and enzyme inhibitory potential of medicinal plant Dryopteris ramosa (Hope) C. Chr.

BACKGROUND: Dryopteris ramosa has numerous potentials uses in the treatment of different maladies as old traditional medication. The fronds of D. ramose are edible and orally administered for producing antibiotic effect. They are also used as astringent and febrifuge, and as a pesticide. METHODS: Extraction of fronds of D. ramosa using solvents of increasing polarity, namely, ethyl acetate, methanol and water were tested for phytochemical (qualitative tests, GC-MS), antimicrobial (well method), antioxidant (DPPH), antifungal (tube dilution), cytotoxic activity (brine shrimps lethality assay) and LOX and COX inhibitory activities were performed using standard methods. RESULTS: The phytochemical analysis of the crude methanolic extract revealed that the fronds are rich in flavonoids, alkaloids, saponins, tannins, glycosides and triterpenoids. The total flavonoid content of the ethyl acetate fraction was 46.28 µg QE/mg extract. The GC-MS analysis revealed nine major compounds that constituted the crude drug and potentially had a role in reported activities. The crude extract was the most active amongst all the fractions against the bacterial and fungal strains used such that it inhibited the growth of P. aeruginosa with a zone of 13 mm and a MIC value of 16 µg/ml as compared to the standard cefixime, which inhibited the zone by only 10 mm and a MIC value of 32 µg/ml. The highest antioxidant potential in DPPH assay was shown by the crude extract with 91.948% free radical scavenging activity. The bring shrimps lethality potential of the crude extract was the highest, with a LD50 value of 47.635 µg/ml. The ethyl acetate fraction inhibits 91.36% of alpha glucosidase enzyme at a concentration of 0.5 mg/ml. In case of acetylcholine esterase inhibition assay, the methanol fraction inhibits 58.26% of the enzyme activity. Similarly, for butyrylcholine esterase inhibition, the maximum inhibitory effect was seen in the methanol fraction, with a percentage inhibition of 47.32%. CONCLUSION: These test results support traditional medicinal uses of the plant. Dryopteris ramosa could be imperative for being used as a therapeutic agent and the medicinal importance of this plant should be further investigated.

[A new phloroglucinol compound from Dryopteris fragrans].

Two phloroglucinol compounds(1-2) were isolated and purified from 95% ethanol extract of Dryopteris fragrans through various column chromatographies on silica gel, Sephadex LH-20, medium pressure column chromatography, and preparative HPLC. Their structures were elucidated as 2',4',6'-trihydroxy-5'-methyl acetate-3'-methyl-1'-butyrophenone(1) and aspidinol B(2) based on their chemical and physicochemical methods and spectroscopic data. Compound 1 is a new phloroglucinol compound named "dryofraginol".

A new phloroglucinol compound from Dryopteris fragrans / 中国中药杂志

Two phloroglucinol compounds(1-2) were isolated and purified from 95% ethanol extract of Dryopteris fragrans through various column chromatographies on silica gel, Sephadex LH-20, medium pressure column chromatography, and preparative HPLC. Their structures were elucidated as 2',4',6'-trihydroxy-5'-methyl acetate-3'-methyl-1'-butyrophenone(1) and aspidinol B(2) based on their chemical and physicochemical methods and spectroscopic data. Compound 1 is a new phloroglucinol compound named "dryofraginol".

In vivo and in vitro anti­allergic and anti­inflammatory effects of Dryopteris crassirhizoma through the modulation of the NF­Ä¸B signaling pathway in an ovalbumin­induced allergic asthma mouse model.

Dryopteris crassirhizoma (DC) has a wide range of pharmacological effects, including antibacterial, anti­influenza virus, anti­tumor, anti­reverse transcriptase and antioxidant effects. However, the inhibitory effect of DC on allergic inflammatory response remains unclear; therefore, the current study used an experimental ovalbumin (OVA)­induced allergic asthma mouse model and phorbol myristate acetate (PMA)­ and A23187­stimulated HMC­1 cells to reveal the effects of DC in regulating airway inflammation and its possible mechanism. Allergic asthma was initiated in BALB/c mice via exposure to OVA emulsified in aluminum, on days 1 and 14. Thereafter, the mice were treated with DC or dexamethasone (Dex) orally, before being challenged, from days 15 to 26. Subsequently, the mice were challenged with OVA on days 27, 28 and 29. The results of histological analysis indicated that the administration of DC decreased the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and suppressed eosinophilic infiltration, mucus production and collagen deposition in the lung tissue. DC treatment increased the level of T helper type 1 (Th1) cytokines (IL­10 and interferon (IFN)­Î³) and decreased the levels Th2 cytokines (IL­4, IL­5 and IL­13) and proinflammatory cytokines (IL­6 and TNF­α). Furthermore, DC treatment inhibited the activation of NF­κB signaling (NF­κB, p­NF­κB, IκB and p­IκB), both in BALF and lung homogenates. Serum levels of total IgE and OVA­specific IgE and IgG1 were significantly lower after DC treatment compared with after OVA treatment. However, the anti­inflammatory effect of OVA­specific IgG2a was higher after DC treatment. In addition, DC treatment attenuated the production of proinflammatory cytokines, including IL­6 and TNF­α, and the activation of NF­κB signaling (NF­κB and p­NF­κB), in PMA and calcium ionophore A23187­stimulated HMC­1 cells. In summary, the current study demonstrated that DC acts a potent anti­allergic and anti­inflammatory drug by modulating the Th1 and Th2 response and reducing the allergic inflammatory reaction in PMA and A23187­stimulated HMC­1 cells via NF­κB signaling in an OVA­induced allergic asthma model.

In Vitro α-glucosidase Inhibition and Computational Studies of Kaempferol Derivatives from Dryopteris cycanida.

BACKGROUND: Dryopteris cycadina has diverse traditional uses in the treatment of various human disorders which are supported by pharmacological studies. Similarly, the phytochemical studies of this plant led to the isolation of numerous compounds. METHODOLOGY: The present study deals with α-glucosidase inhibition of various kaempferol derivates including kaempferol-3, 4/-di-O-α- L-rhamnopyranoside 1, kaempferol-3, 5-di-O-α-L-rhamnoside 2 and kaempferol-3,7-di-O-α- L-rhamnopyranoside 3. RESULTS: The results showed marked concentration-dependent inhibition of the enzyme when assayed at different concentrations and the IC50 values of compounds 1-3 were 137±9.01, 110±7.33, and 136±1.10 mM, respectively far better than standard compound, acarbose 290±0.54 mM. The computational studies revealed strong docking scores of these compounds and augmented the in vitro assay. CONCLUSION: In conclusion, the isolated kaempferol derivatives 1-3 from D. cycadina exhibited potent α- glucosidase inhibition.

Phloroglucinol Derivatives from Dryopteris crassirhizoma as Potent Xanthine Oxidase Inhibitors.

Dryopteris crassirhizoma rhizomes are used as a traditional medicine in Asia. The EtOAc extract of these roots has shown potent xanthine oxidase (XO) inhibitory activity. However, the main phloroglucinols in D. crassirhizoma rhizomes have not been analyzed. Thus, we investigated the major constituents responsible for this effect. Bioassay-guided purification isolated four compounds: flavaspidic acid AP (1), flavaspidic acid AB (2), flavaspidic acid PB (3), and flavaspidic acid BB (4). Among these, 1 showed the most potent inhibitory activity with a half-maximal inhibitory concentration (IC50) value of 6.3 µM, similar to that of allopurinol (IC50 = 5.7 µM) and better than that of oxypurinol (IC50 = 43.1 µM), which are XO inhibitors. A comparative activity screen indicated that the acetyl group at C3 and C3' is crucial for XO inhibition. For example, 1 showed nearly 4-fold higher efficacy than 4 (IC50 = 20.9 µM). Representative inhibitors (1-4) in the rhizomes of D. crassirhizoma showed reversible and noncompetitive inhibition toward XO. Furthermore, the potent inhibitors were shown to be present in high quantities in the rhizomes by a UPLC-QTOF-MS analysis. Therefore, the rhizomes of D. crassirhizoma could be used to develop nutraceuticals and medicines for the treatment of gout.

Total synthesis of dryocrassin ABBA and its analogues with potential inhibitory activity against drug-resistant neuraminidases.

The stems of Dryopteris crassirhizoma, one of the main components of Lianhua-Qingwen Formula (LQF) was traditionally used for heat-clearing and detoxifying. Dryocrassin ABBA is a key antiviral component in the herbal medicine while the compound is hard to get in large amounts with the features of homologous compounds, polyphenol groups, and low contents. Therefore, the present work aims to seek influenza H7N9 virus inhibitors from natural source by synthesis of dryocrassin ABBA and its analogues. As a result, total synthesis of the compound was achieved in nine steps with an over-all yield of 4.6%. Neuraminidases (NAs) inhibitory activities of the synthesized product and its analogues were evaluated afterward. Comparing with the positive control, OSV (9.6 µM), it was very exciting that dryocrassin ABBA and its analogues (b5 and e2) showed better NAs inhibitory activity against Anhui H7N9 with IC50 values of 3.6 µM, 2.5 µM and 1.6 µM. For the highly resistant Shanghai N9, these compounds can also show medium inhibitory activities. Docking results indicated the direct interaction of synthesized 3 hits with the key K294 by hydrogen bonds, but no direct interaction of OSV with the key K294 was observed in Shanghai N9. This study suggested that dryocrassin ABBA and its analogues especially AB, which consisted of polyphenol groups may have beneficial effects on treating avian influenza H7N9 virus.