Altenuene derivatives produced by an endophyte Alternaria alternata.

Two novel aromatic polyketides 1 and 3 and five known compounds, (4S,10S)-talaroflavone (2), altenuene (4), isoaltenuene (5), alternariol (6), and altenusin (7), were isolated from an endophytic strain of Alternaria alternata SI-694. The structures of the new compounds, including their absolute configurations, were elucidated by NMR, IR, UV, and ECD spectroscopies, and the phytotoxicities of the isolated compounds were also evaluated. Altenusin (7) showed moderate cytotoxicity against HL-60 cells, with an IC50 of 6.65 µM, whereas 5, 6, and 7 were phytotoxic against Lactuca sativa, Brassica campestris L., Stellaria aquatica (L.) Scop. and Digitaria ciliaris.

Golden berry leaf extract containing withanolides suppresses TNF-α and IL-17 induced IL-6 expression in HeLa Cells.

Inflammation, characterized by the overexpression of IL-6 in various tissues, has been reported as a symptom of coronavirus disease 2019. In this study, we established an experimental system for overexpression of IL-6 in HeLa cells stimulated by TNF-α and IL-17, along with identification of anti-inflammatory materials and components from local agricultural, forestry, and fishery resources. We constructed a library of extracts from natural sources, of which 111 samples were evaluated for their anti-inflammatory activities. The MeOH extract of Golden Berry (Physalis peruviana L) leaf was found to exhibit strong anti-inflammatory properties (IC50 = 4.97 µg/mL). Preparative chromatography identified two active constituents, 4ß-hydroxywithanolide E (4ß-HWE) (IC50 = 183 nM) and withanolide E (WE) (IC50 = 65.1 nM). Withanolides are known anti-inflammatory ingredients of Withania somnifera, an Ayurvedic herbal medicine. P. peruviana leaves containing 4ß-HWE and WE should be considered as useful natural resources for anti-inflammatory products.

Dihydroisocoumarins of Hydrangea macrophylla var. thunbergia inhibit binding of the SARS-CoV-2 spike protein to ACE2.

Binding of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the cognate angiotensin-converting enzyme 2 (ACE2) receptor is the initial step in the viral infection process. In this study, we screened an in-house extract library to identify food materials with inhibitory activity against this binding using enzyme-linked immunosorbent assays and attempted to ascertain their active constituents. Hydrangea macrophylla var. thunbergia leaves were identified as candidate materials. Its active compounds were purified using conventional chromatographic methods and identified as naringenin, dihydroisocoumarins, hydrangenol, and phyllodulcin, which have affinities for the ACE2 receptor and inhibit ACE2 receptor-spike S1 binding. Given that boiled water extracts of H. macrophylla leaves are commonly consumed as sweet tea in Japan, we speculated that this tea could be used as a potential natural resource to reduce the risk of SARS-CoV-2 infection.

Anti-melanogenic effect of furanoeremophilanes identified from edible wild plants belonging to the genus Cacalia.

Cacalia delphiniifolia and Cacalia hastata are edible wild plants in Japan. We found that these plants have anti-melanogenic activity in B16F10 mouse melanoma cells. Three furanoeremophilanes, cacalol (from C. delphiniifolia), dehydrocacalohastin, and cacalohastin (from C. hastata), were identified as the main active components. The genus Cacalia may be a good source of beneficial materials with anti-melanogenic effects.

Petasin is the main component responsible for the anti-adipogenic effect of Petasites japonicus.

Petasites japonicus is one of the most popular edible wild plants in Japan. Many biological effects of P. japonicus have been reported, including anti-allergy, anti-inflammation, and anticancer effects. Although its anti-obesity effect has been reported in several studies, the most important component responsible for this activity has not been fully elucidated. On screening the components that suppress adipocyte differentiation in 3T3-F442A cells, we found that the extract of the flower buds of P. japonicus has anti-adipogenic effect. Among the known major components of P. japonicus, petasin exhibited a potent anti-adipogenic effect at an IC50 value of 0.95 µM. Quantitative analysis revealed that the active component responsible for most of the anti-adipogenic effects of P. japonicus extract is petasin. Petasin suppressed the expression of markers of mature adipocytes (PPARγ, C/EBPα, and aP2). However, as isopetasin and petasol, analogs of petasin, did not exhibit these effects, it indicates that a double bond at the C11-C12 position and an angeloyl ester moiety were essential for the activity. Petasin affected the late stage of adipocyte differentiation and inhibited the expression of lipid synthesis factors (ACC1, FAS, and SCD1). Additionally, it was revealed that petasin could be efficiently extracted using hexane with minimal amount of pyrrolizidine alkaloids, the toxic components. These findings indicate that P. japonicus extract containing petasin could be a promising food material for the prevention of obesity.

Antioxidant p-terphenyl compound, isolated from edible mushroom, Boletopsis leucomelas.

A new acetyl p-terphenyl derivative, boletopsin 15, was isolated from the ethyl acetate extract of fruit bodies of the Basidiomycete Boletopsis leucomelas, together with 4 known compounds. The structures of these compounds were elucidated by spectral analysis as well as by directly comparing the spectral data of the new compound with those of known compounds. The free radical-scavenging activity of the compounds was assayed using the 2,2-diphenyl-1-picrylhydrazyl scavenging method. The results showed that compounds 1 and 2 exhibited significant antioxidant activity (1: EC50 = 2.1 µm and 2: EC50 = 6.6 µm).

A yeast-based screening system identified bakkenolide B contained in Petasites japonicus as an inhibitor of interleukin-2 production in a human T cell line.

Ca2+ signaling is related to various diseases such as allergies, diabetes, and cancer. We explored Ca2+ signaling inhibitors in natural resources using a yeast-based screening method and found bakkenolide B from the flower buds of edible wild plant, Petasites japonicus, using the YNS17 strain (zds1Δ erg3Δ pdr1/3Δ). Bakkenolide B exhibited growth-restoring activity against the YNS17 strain and induced Li+ sensitivity of wild-type yeast cells, suggesting that it inhibits the calcineurin pathway. Additionally, bakkenolide B inhibited interleukin-2 production at gene and protein levels in Jurkat cells, a human T cell line, but not the in vitro phosphatase activity of human recombinant calcineurin, an upstream regulator of interleukin-2 production. Furthermore, bakkenolide A showed weak activity in YNS17 and Jurkat cells compared with bakkenolide B. These findings revealed new biological effects and the structure-activity relationships of bakkenolides contained in P. japonicus as inhibitors of interleukin-2 production in human T cells.

Synthesis of low-molecular weight fucoidan derivatives and their binding abilities to SARS-CoV-2 spike proteins.

Fucoidan derivatives 10-13, whose basic sugar chains are composed of repeating α(1,4)-linked l-fucopyranosyl residues with different sulfation patterns, were designed and systematically synthesized. A structure-activity relationship (SAR) study examined competitive inhibition by thirteen fucoidan derivatives against heparin binding to the SARS-CoV-2 spike (S) protein. The results showed for the first time that 10 exhibited the highest inhibitory activity of the fucoidan derivatives used. The inhibitory activity of 10 was much higher than that of fondaparinux, the reported ligand of SARS-CoV-2 S protein. Furthermore, 10 exhibited inhibitory activities against the binding of heparin with several mutant SARS-CoV-2 S proteins, but was found to not inhibit factor Xa (FXa) activity that could otherwise lead to undesirable anticoagulant activity.

Eosinophilic cellulitis as a cutaneous manifestation of idiopathic hypereosinophilic syndrome.

Three patients with eosinophilic cellulitis associated with sustained peripheral blood eosinophilia of unidentified cause are reported. They also presented with diversities of extracutaneous symptoms such as bronchospasm, sensory polyneuropathies, epigastralgia, and gangrenous eosinophilic enteritis. These cases suggest that eosinophilic cellulitis can develop as a cutaneous manifestation of idiopathic hypereosinophilic syndrome.

Relapsing coalescent papular dermatosis of elderly patients: a precursor or an abortive lesion of Ofuji papuloerythroderma.

We describe a group of elderly patients (average: 71.1 year-old, 37 male and 6 female patients) with relapsing, coalescent, papular dermatosis. The skin rash started as intensely pruritic, discrete, solid papules developing in crops in a fairly localized area. The primary papular lesions tended to coalesce into flat-topped, polygonal papules or plaques that often showed a cobble stone-like appearance. The disease took a protracted course of repeated relapses without known precipitating factors. Both papular and coalescent plaque lesions showed compact perivascular infiltration of mononuclear cells containing varying populations of eosinophils in the upper dermis. Approximately half of the patients had mild hypereosinophilia and elevated serum IgE levels without histories of atopic diathesis. These clinicopathological features were consistent with those of the papular lesions that Ofuji originally defined as the primary skin rash of papuloerythroderma. We propose that our cases represent a precursor or an abortive lesion of Ofuji papuloerythroderma.

Japanese spotted fever involving the central nervous system: two case reports and a literature review.

Japanese spotted fever (JSF), first reported in 1984, is a rickettsial disease caused by Rickettsia japonica. Until now, affliction of the central nervous system has been rarely reported. Here we report two cases of JSF associated with a central nervous system disorder such as meningoencephalitis.

Short-term etretinate therapy for prurigo chronica multiformis.

Prurigo chronica multiformis is an intensely pruritic, chronic cutaneous disorder of unknown etiology without any effective treatment. This is a report on the results of using etretinate therapy to treat prurigo chronica multiformis. Thirty-seven patients (average age; 69.1+/-11.5 year-old) were treated with 30 mg/day etretinate along with topical steroids (very strong classes) and oral antihistamines. Etretinate was discontinued as soon as remission was achieved. Thirty-six patients were followed up for at least four weeks. The number of patients who achieved remission increased progressively after the initiation of etretinate therapy; 18 patients were totally and 14 were partially free of active skin lesions within four weeks. Eventually, 27 patients achieved remission with an average duration of 4.4+/-3.1 weeks etretinate treatment (range; 1-14 weeks), and five achieved partial remission. Four patients discontinued etretinate within two weeks because of the absence of clinical response (two cases) or exacerbation of the skin lesion (two cases). Among the 27 patients who had achieved remission, 23 had recurrence after the cessation of etretinate. The remission period ranged from 1 to 32 weeks with an average duration of 5.7+/-6.7 weeks. Combined treatment with topical steroids and oral antihistamines did not achieve remission in the recurrent cases but re-administration of 30 mg/day etretinate did. Our observation suggests that a moderate dose of etretinate is a safe and effective therapy for prurigo chronica multiformis, which is often resistant to conventional treatment using topical steroids and oral antihistamines.