In vitro anti-severe acute respiratory syndrome coronavirus 2 effect of Ephedra przewalskii Stapf extract.

ETHNOPHARMACOLOGICAL RELEVANCE: The terrestrial stems of Ephedra (Ephedra spp.; including Ephedra sinica Stapf and Ephedra przewalskii Stapf) extracts are used in traditional medicines in East Asia. In Japan, the Kampo formula containing E. sinica extract is prescribed for the treatment of the common cold, influenza virus infections, and mild symptoms of coronavirus disease 2019 (COVID-19). Although ephedrine alkaloids in E. sinica exert antitussive effects, they may have side effects associated with the sympathetic nervous system. E. przewalskii extract, a drug used in traditional Uyghur and Mongolian medicine, is considered to be free of ephedrine alkaloids and is a promising candidate for the treatment of infectious diseases. However, its use is currently limited because evidence of its antiviral efficacy remains inconclusive. AIM OF THE STUDY: We compared the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effects of E. przewalskii and E. sinica extracts in vitro. Additionally, we examined the differences in their antiviral effects against different SARS-CoV-2 strains. MATERIALS AND METHODS: VeroE6/TMPRSS2 cells were infected with SARS-CoV-2 (Conventional, Delta, and Omicron strains-BA.1, BA.2, BA.4, and BA.5), and lysates prepared from each herbal extract were added. The infectious titer was determined using the 50% tissue culture infectious dose (TCID50) method; in turn, the half-maximal inhibitory concentration (IC50) was calculated for each extract to compare the antiviral efficacy of E. sinica and E. przewalskii extracts. Further, the extracts were compared with remdesivir for their antiviral efficacy against the conventional viral strain. To verify the effect of the inactivation of virus particles, these extracts were added to each SARS-CoV-2 strain, and the infectious titers were determined using the TCID50 method. RESULTS: The antiviral efficacy (i.e., IC50) of the E. przewalskii extract against each SARS-CoV-2 strain was 2.7-10.8-fold greater than that of the E. sinica extract. The antiviral efficacy of the E. przewalskii extract against conventional viral strains was compared with that of remdesivir, which was 1/27.6 of remdesivir's efficacy. The E. sinica extract showed minimal inactivation of virus particles of each strain, whereas the E. przewalskii extract resulted in substantial viral inactivation. CONCLUSIONS: The E. przewalskii extract showed higher antiviral activity against SARS-CoV-2 than the E. sinica extract. Overall, our study suggests that E. przewalskii extract can be used for the treatment of viral infections, including COVID-19.

New diterpenes from Nigella damascena seeds and their antiviral activities against herpes simplex virus type-1.

Nigella species are rich source of dolabellane diterpenes. During our study of Nigella species, new dolabellane diterpenes, damasterpenes V-VIII were isolated. The structural determination of new compounds damasterpenes V-VIII is described with consideration of their absolute configurations. The antiviral activities against herpes simplex virus type-1 of the isolated compounds and their derivatives are also evaluated. Damasterpene V (inhibition 35.0%) and 2-phenylacetyl 13-benzoyl damasterpenol (32.0%) showed significant antiviral activity at 10 µM.

Neolignan and megastigmane glucosides from the aerial parts of Isodon japonicus with cell protective effects on BaP-induced cytotoxicity.

Six neolignan glucosides, named isodonosides I-VI, and a megastigmane glucoside named isodonmegastigmane I, were isolated together with 15 known compounds from the methanolic extract of aerial parts of Isodon japonicus cultivated in Tokushima, Japan. The chemical structures of the compounds were elucidated based on their MS and NMR spectroscopic analysis. The absolute configurations of the neolignan and megastigmane glucosides were determined by derivatizations, by ECD (electronic circular dicroism) Cotton effect approximation, and by the modified Mosher's method. In addition, a significant cell protective effects of neolignan glucosides on benzo[a]pyrene-induced cytotoxicity was found.

Efficacy of Japanese traditional (Kampo) medicine for treating chemotherapy-induced peripheral neuropathy: A retrospective case series study.

AIM: To investigate Japanese traditional (Kampo) medicine's effectiveness on cancer chemotherapy-induced peripheral neuropathy (CIPN), we carried out this retrospective study. METHODS: By searching our outpatient database of 3154 patients who consulted our outpatient clinic of Japanese-Oriental (Kampo) Medicine at Chiba University Hospital from November 2005 to December 2010, a total of 281 patients diagnosed with cancer were identified. Twenty-four patients out of the 281 patients identified met the following three conditions and were eligible for further investigation of the effectiveness of Kampo treatment: At least one course of cancer chemotherapy had been administered; numbness and pain appeared after the chemotherapy; and CIPN was diagnosed before they were given Kampo treatment. RESULTS: The 24 patients included 6 males and 18 females and ranged in age from 39 to 86 (mean 61.2 ± 11.5) years old. Kampo formulas were individually chosen by Kampo expert doctors based on Kampo-specific diagnostics. Beneficial outcomes were obtained by Kampo treatment in 20 out of the 24 cases (83.3%). Nine out 20 cases had a major response (the numbness and pain showed improvement or reduction by 50% or more), with 7 of 9 cases showing a more than 70% symptom reduction. Eleven out of 20 cases showed a minor response (less than 50% symptom reduction), and 4 out of the 24 cases had no beneficial response. The most frequently used formula was goshajinkigan (GJG), followed by hachimijiogan (HJG) and keishibukuryogan. Thirteen of the 24 cases (54.2%) were prescribed aconite root-containing formulas including GJG and HJG. Aconite root has "warming" effects and ameliorates pain and numbness; 21 out of 24 cases (87.5%) in total used warming formulas such as aconite root-containing formulas to reduce CIPN. CONCLUSION: Our current study suggested that Kampo formulas chosen based on Kampo-specific diagnostics could be for treating CIPN that is refractory to conventional medicine.

Analysis and Management of Rectal Gas with Kampo Formulas During Intensity-Modulated Radiotherapy of Prostate Cancer: A Case Series Study.

OBJECTIVES: During intensity-modulated radiation therapy (IMRT) for prostate cancer, the target, bladder, and rectum positions should be kept constant to reduce adverse events, such as radiation proctitis, and to increase local tumor control. For this purpose, decreasing the rectal contents as much as possible is important. Daisaikoto (DST) and bukuryoingohangekobokuto (BIHKT) are traditional Japanese herbal (Kampo) formulas that have been used to treat patients with abdominal bloating or constipation. MATERIALS AND METHODS: This study investigated the effect of DST and BIHKT on the rectal gas volume during prostate IMRT according to Kampo diagnosis. Five patients were treated with DST or BIHKT at a dose of 5.0 or 7.5 g/d. The volume of rectal gas in 189 megavoltage computed tomographic images taken before each treatment session and the frequency of rectal gas drainage were evaluated before and after DST or BIHKT administration. RESULTS: After DST or BIHKT treatment, the mean volume of rectal gas was reduced from 6.4 to 2.1 mL, and the mean frequency of gas drainage decreased from 43% to 9%. CONCLUSIONS: DST and BIHKT appear to be useful in reducing rectal gas, which would help prevent radiation proctitis and improve the local control of prostate cancer with IMRT.

γ-Lactam alkaloids from the flower buds of daylily.

Four new alkaloids, hemerocallisamines IV-VII, were isolated from the methanol extract of flower buds of daylily. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The absolute stereochemistry of the hemerocallisamines IV-VI was elucidated by the application of the modified Mosher's method, HPLC analysis, and optical rotation. In the present study, the isolated alkaloids significantly inhibited the aggregation of Aß42 in vitro. This is the first report about bioactive alkaloids with a γ-lactam ring from daylily. In addition, isolated nucleosides showed accelerative effects on neurite outgrowth under the non-fasting condition.

Structure of a Coumaric Acid Analogue with a Monoterpene Moiety from the Flowers of Osmanthusfragrans var. aurantiacus and Evaluation of Cinnamic Acid Analogues as Nitric Oxide Production and Degranulation Inhibitors.

A coumaric acid analogue with a monoterpene moiety named floraosmanol A (1) was isolated from the flowers of Osmanthisfragrans var. aurantiacus. The chemical structure was elucidated on the basis of chemical and physicochemical evidence. Floraosmanol A (1) significantly inhibited nitric oxide .(NO) production in lipopolysaccharide- (LPS) activated RAW264.7 macrophages and the release of P-hexosaminidase as a marker of degranulation from rat basophile leukemia (RBL-2H3) cells. In addition, several cinnamic acid analogues were conjugated with geraniol and 3-methyl-2-buten-1-ol through an ester linkage. The inhibitory effects on NO production and the release of P-hexosaminidase of the synthesized compounds were examined for structure-activity relationships.

"Ninjinto" (Ginseng Decoction), a Traditional Japanese Herbal Medicine, Improves Gastrointestinal Symptoms and Immune Competence in Patients with Chronic Intestinal Failure.

Background. Treating functional gastrointestinal disorders is extremely difficult. We herein report the effect of the oral administration of Ninjinto (NJT, ginseng decoction), a traditional Japanese Kampo medicine, on chronic intestinal failure. Patients and Methods. Seven patients with chronic intestinal failure treated with NJT were evaluated in this study. The primary diseases included chronic intestinal pseudoobstruction (CIPO: n = 4), short bowel syndrome (SBS: n = 2), and intestinal atresia (n = 1). All patients orally received NJT extract granules at a dose of 0.3 g/kg BW per day. The treatment outcomes were then assessed according to the patients' symptoms and consecutive abdominal X-ray findings. Results. The targeted symptoms were abdominal distension in four patients, diarrhea in three patients, and frequent hospitalization due to infections in two patients. An improvement in the symptoms was observed in six of the seven patients, whereas one patient with SBS did not show any improvement. An improvement in an abdominal roentgenogram was observed in the four patients with remarkably dilated bowel loops due to CIPO. Conclusions. NJT may be effective in controlling functional gastrointestinal disorders associated with chronic intestinal failure. The use of Kampo medicine in the field of pediatric surgery may help to improve the quality of life in children suffering from such conditions.

Chemical structures of constituents from the flowers of Osmanthus fragrans var. aurantiacus.

Three new megastigmane glycosides named floraosmanosides I-III and a new γ-decalactone named floraosmanolactone I together with 16 known constituents were isolated from the flowers of Osmanthus fragrans var. aurantiacus cultivated in Guangxi Zhuang Autonomous Region, China. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. Among them, ligustroside and (+)-pinoresinol significantly inhibited nitric oxide production in lipopolysaccharide-activated RAW264.7 macrophages.

Structure of diarylheptanoids with antiallergic activity from the rhizomes of Curcuma comosa.

The methanolic extract from the dried rhizomes of Curcuma comosa cultivated in Thailand was found to inhibit the release of ß-hexosaminidase as a maker of degranulation from rat basophil leukemia (RBL-2H3) cells. Two new diarylheptanoids, diarylcomosols IV and V, were isolated from the methanolic extract. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The isolated diarylheptanoids showed inhibitory activity, and the structural requirements of the active constituents for the inhibition were clarified.

Structure of constituents isolated from the flower buds of Cananga odorata and their inhibitory effects on aldose reductase.

Three new terpenoid derivatives, canangaterpenes IV-VI, were isolated from the flower buds of Cananga odorata, cultivated in Thailand, together with eight known flavonoids. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated compounds on aldose reductase were also investigated. Several terpenoid derivatives and flavonoids were shown to inhibit aldose reductase.

Structures of acylated sucroses from the flower buds of Prunus mume.

Seven new acylated sucroses, mumeoses P-V, were isolated from the flower buds of Prunus mume, cultivated in Zhejiang province, China. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence. Moreover, mumeoses C, D, and R, were shown to substantially inhibit aldose reductase.

Effectiveness of traditional Japanese herbal (kampo) medicine, daiobotanpito, in combination with antibiotic therapy in the treatment of acute diverticulitis: a preliminary study.

In traditional Japanese herbal (Kampo) medicine, daiobotanpito (DBT) or Da Huang Mu Dan Tang in Chinese has been used in medical treatment of acute diverticulitis for many years based on the experience. Our aim was to investigate whether the treatment of acute diverticulitis can be treated with intravenous antibiotics plus orally administrated DBT than intravenous antibiotics alone. A retrospective nonrandomized open-label trial was established to compare patients with acute diverticulitis who received oral DBT associated with intravenous antibiotics with those who received intravenous antibiotic alone. We included 34 patients, eleven patients in group 1 with DBT and 23 patients in group 2 without DBT. Both groups were comparable in patient demographics and clinical characteristics. There was a significantly better outcome in the group treated with DBT than in the group without DBT when comparing duration of fever, abdominal pain, and antibiotics administration. A trend toward a day shorter mean hospital stay and fasting was seen in group 1, although this did not reach statistical significance. In conclusion, most patients with acute diverticulitis can be managed safely with oral DBT. Although randomized, double-blind study must be done, we could show the possibility to use daiobotanpito as an additional option in treating acute diverticulitis.

Therapeutic effects of saireito (chai-ling-tang), a traditional Japanese herbal medicine, on lymphedema caused by radiotherapy: a case series study.

Despite the development of radiotherapy machines and technologies, a proportion of patients suffer from radiation-induced lymphedema. Saireito (SRT) is a traditional Japanese herbal medicine that has been used for treating edema and inflammation in conditions such as nephritic disease. This study investigated the effect of SRT on lymphedema caused by radiotherapy. Four patients were treated with SRT at a dose of 9 g/day. The severity of lymphedema was evaluated using the Common Terminology Criteria for Adverse Events version 4 and Numerical Rating Scale before and after SRT treatment. After the treatment with SRT, 2 of 4 patients (50%) showed apparent improvement in lymphedema. One of the cases had difficulty in wearing the custom-made thermoplastic cast, but after SRT administration, he could wear the mask easily. One case decided to stop taking SRT 3 days after initiation because cough and fever appeared. In conclusion, it is important to control the side effects of radiotherapy, which leads to improved tumor control rates. Prospective randomized studies are necessary to confirm the findings of this case series study.

Efficacy of contact needle therapy for chemotherapy-induced peripheral neuropathy.

Cancer chemotherapy-induced peripheral neuropathy (CIPN) often results in discontinuation of treatment with potentially useful anticancer drugs and may deteriorate the patient's quality of life. This study investigated the effect of contact needle therapy (CNT) on CIPN caused by responsible chemotherapeutic agents as taxanes and oxaliplatin. Six patients with CIPN were treated with CNT. The severity of CIPN was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 4 and FACT/GOG-Ntx before and after CNT. After the treatment, all of the patients showed some improvement. Four patients showed apparent improvement in breakthrough pain. One of the cases had difficulty in walking because of CIPN in lower extremities, but after 2 times of CNT, he could walk without pain and could continue the chemotherapy. Although its putative mechanisms remain elusive, CNT has strong potential as an adjunctive therapy in CIPN. Well-designed clinical trials with adequate sample size and power are necessary to confirm the findings of this study.

Medicinal flowers. XXXVIII. structures of acylated sucroses and inhibitory effects of constituents on aldose reducatase from the flower buds of Prunus mume.

The methanolic extract from the flower buds of Prunus mume, cultivated in Zhejiang province, China, showed an inhibitory effect on aldose reductase. From the methanolic extract, five new acylated sucroses, mumeoses F-J, were isolated together with 29 known compounds. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated compounds on aldose reductase were also investigated. Acylated quinic acid analogs, which are one of the major compounds of the flower buds of P. mume, were shown to substantially inhibit aldose reductase. In particular, mumeic acid-A was found to exhibit a potent inhibitory effect [IC50=0.4 µm].

Structures of acylated sucroses and an acylated flavonol glycoside and inhibitory effects of constituents on aldose reductase from the flower buds of Prunus mume.

Five new acylated sucroses, mumeoses K-O, and a new acylated flavonol glycoside, mumeflavonoside A, were isolated from the flower buds of Prunus mume, cultivated in Zhejiang province, China. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated acylated sucroses and flavonol glycosides on aldose reductase were also investigated. Several flavonol glycosides including mumeflavonoside A were shown to inhibit aldose reductase.

Alkaloids from Sri Lankan curry-leaf (Murraya koenigii) display melanogenesis inhibitory activity: structures of karapinchamines A and B.

A methanolic extract and its ethyl acetate-soluble fraction from Sri Lankan curry-leaf, the leaves of Murraya koenigii, inhibited melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Two new carbazole alkaloids, karapinchamines A and B, were isolated from the ethyl acetate-soluble fraction together with 12 known carbazole alkaloids. The structures of karapinchamines A and B were determined by physicochemical analyses. The principal alkaloid constituents were found to display potent melanogenesis inhibitory activity. The structural requirements of the carbazole alkaloids for melanogenesis inhibitory activity were discussed.