Search

Baicalin and berberine are biologically active constituents of the crude drugs Scutellaria root and Coptis rhizome/Phellodendron bark, respectively. Baicalin and berberine are reported to combine together as a 1:1 complex that forms yellow precipitates by electrostatic interaction in decoctions of Kampo formulae containing these crude drugs. However, the structural basis and mechanism for the precipitate formation of this compound-compound interaction in aqueous solution remains unclarified. Herein, we searched for berberine derivatives in the Coptis rhizome that interact with baicalin and identified the chemical structures involved in the precipitation formation. Precipitation assays showed that baicalin formed precipitates with berberine and coptisine but not with palmatine and epiberberine. Thus, the 2,3-methylenedioxy structure may be crucial to the formation of the precipitates, and electrostatic interaction is necessary but is not sufficient. In this multicomponent system experiment, palmatine formed a dissociable complex with baicalin and may competitively inhibit the formation of berberine and coptisine precipitation with baicalin. Therefore, the precipitation formed by berberine and baicalin was considered to be caused by the aggregation of the berberine-baicalin complex, and the 2,3-methylenedioxy structure is likely crucial to the aggregation of the complex., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

A search for anti-trypanosomal natural compounds from plants collected in El Salvador, a country particularly endemic for Chagas disease, resulted in the isolation of five lignan-type compounds ( 1 - 5 ) from Peperomia pseudopereskiifolia . The lignan derivatives 1 , 2 , and 4 are new. Their absolute configuration was determined by chemical derivatization. Compounds 1 , 5 , 6 , and 8 exhibited anti-trypanosomal activity against the amastigote form of T. cruzi comparable to that of the existing drug benznidazole.

Introduction: Standardization is an import factor in ensuring the safety, efficacy, and quality of herbal medicines, and facilitates their international commerce. Heavy metal poisoning due to herbal medicines has been reported in many countries. Here, to better understand the current state of harmonization, we compared regulations for arsenic and heavy metals in herbal medicines across seven countries and two regions with two international standards., Methods: We studied the monographs of herbal medicines of seven countries and two regions, as well as the WHO guidelines and ISO standards. We then compared the limits and test methods adopted for elemental impurities in herbal medicines listed in the monographs and standards among countries., Results: The number of herbal medicines assessed amounted to over 2000. Limits and test methods adopted for elemental impurities in herbal medicines varied by country/region and organization. Although WHO recommends a uniform upper limit for lead and cadmium for all herbal medicines, some countries set unique upper limits for individual herbal medicines. ISO 18664:2015 lists only instrumental analysis methods, whereas Japan and India list only chemical methods., Conclusions: Many countries do not adhere to the WHO or ISO recommendations on elemental impurities in herbal medicines. These findings suggest the presence of differences in regulations for herbal medicines among countries/regions, likely rooted in cultural differences and policies aimed at maintaining the diversity of herbal medicines. Regulatory convergence by "loose harmonization" to internationally agreed standards appears a feasible option to maintain diversity and safety, and promote international trade in herbal medicines., (© 2023. The Author(s).)

Objective: Despite the development of newly developed drugs, most multiple myeloma (MM) patients with high-risk cytogenetic abnormalities such as t(4;14) or del17p relapse at anin early stage of their clinical course. We previously reported that a natural product,komaroviquinone (KQN), isolated from the perennial semi-shrub Dracocephalum komarovi, i.e., komaroviquinone (KQN) and its derivative GTN024 induced the apoptosis of MM cells by producing reactive oxygen species (ROS), but both exhibited significant hematological toxicity. Aim of this study is to clarify anti-tumor activity, safety and pharmacokinetics of GTN057, an optimization compound of KQN in vivo., Methods: ICR/SCID xenograft model of KMS11, a t(4;14) translocation-positive MM cell line, was used for in vivo study. Mice pharmacokinetics of GTN057 and the degradation products were analyzed by LC-MS/MS., Results: Herein, our in vitro experiments revealed that GTN057 is much less toxic to normal hematopoietic cells, induced the apoptosis of both MM cell lines andpatient samples, including those with high-risk cytogenetic changes. A xenograft model of a high-risk MM cell line demonstrated that GTN057 significantly delayed the tumor growth with no apparent hematological or systemic toxicities in vivo. The pathological examination of GTN057-treated tumors in vivoshowed revealed apoptosis of MM cells and anti-angiogenesis. In addition to the production of ROS, GTN057 inhibited the downstream signaling of c-MET, a receptor tyrosine kinase a receptor forand hepatocyte growth factor (HGF) receptor. Thus, GTN057 is less toxic and is able tomay be a candidate drug for treating MM patients, via multifunctional mechanisms. We have also extensively studied the pharmacologyical analysis of GTN057. The metabolites of GTN057, (e.g.,such as GTN054), may also have anti-tumorantitumor activity., Conclusion: Natural products or and their derivatives can could be good sources of antineoplastic drugs even for high-risk cancer., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Achyranthes root is a crude drug used as diuretic, tonic and remedy for blood stasis. Characteristic oleanolic acid saponins with a dicarboxylic acid moiety have been isolated as one of the representative constituents of this crude drug. This review focuses on the triterpene saponin constituents, especially those with a characteristic dicarboxylic acid moiety, of A. bidentata and A. fauriei. Several groups isolated the saponins and different names were given to one compound in some cases. The names of the compounds are sorted out and the stereochemistry of the dicarboxylic acid moieties are summarized. HPLC analysis of the composition of the saponin constituents and the effect of processing and extraction conditions on the composition are reviewed. Biological activities of the saponin constituents are also summarized., (© 2021. The Author(s).)

Methylophiopogonanone A (MOPNA, 1) is a characteristic homoisoflavonoid, having two methyl groups on the A ring, isolated from Ophiopogon Root (enlarged part of the root of Ophiopogon japonicus Ker-Gawler, Liliaceae). Although MOPNA is chemically stable in various organic solvents, such as acetone, chloroform, methanol and dimethyl sulfoxide, it gave a spot of higher polarity in addition to the spot of MOPNA on the surface of TLC plate. The spot was isolated and the structure of the major compound was revealed to be a compound with an oxygen atom at C-6 of the A ring. This oxidation on the surface of TLC plate was observed for synthetic intermediates of MOPNA having two methyl groups on a phloroacetophenone-type ring, suggesting that the methyl groups enhanced susceptibility to air oxidation. The structure of the major oxidation product was similar to those of humulone and sufflomin A. Humulone has two prenyl units and sufflomin A has two C-glucosyl moieties instead of the two methyl groups, respectively. As dialkylated phloroacetophenone derivatives seem susceptible to oxidation, air oxidation might be involved in the formation of these compounds., (© 2022. The Japanese Society of Pharmacognosy.)

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and in Central America, it is considered one of the four most infectious diseases. This study aimed to screen the anti-trypanosomal activity of plant species from Salvadoran flora. Plants were selected through literature search for plants ethnobotanically used for antiparasitic and Chagas disease symptomatology, and reported in Museo de Historia Natural de El Salvador (MUHNES) database. T. cruzi was incubated for 72 h with 2 different concentrations of methanolic extracts of 38 species, among which four species, Piper jacquemontianum, Piper lacunosum, Trichilia havanensis, and Peperomia pseudopereskiifolia, showed the activity (≤ 52.0% viability) at 100 µg/mL. Separation of the methanolic extract of aerial parts from Piper jacquemontianum afforded a new flavanone (4) and four known compounds, 2,2-dimethyl-6-carboxymethoxychroman-4-one (1), 2,2-dimethyl-6-carboxychroman-4-one (2), cardamomin (3), and pinocembrin (5), among which cardamomin exhibited the highest anti-trypanosomal activity (IC 50  = 66 µM). Detailed analyses of the spectral data revealed that the new compound 4, named as jaqueflavanone A, was a derivative of pinocembrin having a prenylated benzoate moiety at the 8-position of the A ring., (© 2021. The Author(s).)

In order to investigate the relationship between the chemical composition of essential oils and haplotypes of the psbA-trnH intergenic spacer region of chloroplast DNA (psbA-trnH) in Valerianae Fauriei Radix (Japanese Valerian; JV), we analyzed the DNA sequence and GC-MS metabolome of JV from Japanese markets and of herbal specimens from related species. DNA analysis revealed that JV products from Japan consisted of three haplotypes, namely AH-1, -2 and -5 reported in our previous study. The GC-MS metabolome revealed five chemotypes (J 1 , J 2 , C, K and O), of which J 1 , J 2 and C were detected in the JV products from Japan. Chemotypes J 1 and J 2 , with kessyl glycol diacetate (KGD) as the main volatile component, were found in the products of Japanese origin whereas chemotype C, with 1-O-acetyl-2,10-bisaboladiene-1,6-diol (ABD), was found in the products of Chinese and Korean origin. The haplotypes were correlated with the chemotypes: haplotype AH-1 for chemotype J 1 , AH-2 for chemotype J 2 and AH-5 for chemotype C, suggesting that the chemical diversity of JV is not attributed to the environmental factors rather to the genetic factors. Since KGD and ABD were reported to have sedative effects and nerve growth factor (NGF)-potentiating effects, respectively, understanding the chemotypes and selecting an appropriate one would be important for the application of JV. The psbA-trnH haplotypes could be useful DNA markers for the quality control and standardization of JV.

Natural medicines, including crude drugs and Kampo prescriptions, have a long history of clinical uses. An important characteristic of natural medicines is that they are multicomponent medicines. Kampo prescriptions, particularly, usually consist of several crude drugs that contain a large number of constituents. The therapeutic effects of a Kampo prescription result from the total effects of its constituents and not from the effect of a representative constituent with a strong pharmacological effect. In fact, only a few of these constituents with strong biological activity have been listed in the Japanese Pharmacopoeia as therapeutic agents. During my research career, I have observed various synergistic effects and interactions among the constituents of natural medicines. This article reviewed our researches on the biologically active constituents of natural medicines, including the analysis of the anti-inflammatory constituents of orengedokuto (a Kampo prescription). Understanding the role of each constituent with therapeutic effects in Kampo prescriptions forms a scientific basis of Kampo medicine. This will enable the better use and quality control of Kampo prescriptions. Moreover, this will aid the future development of a multicomponent mimic for a specific effect of a Kampo prescription using the appropriate mixture of active constituents in amounts found in the prescription. The above is my dream as a natural product chemist, and I believe that the mixture can do more than we anticipate!

Stereocontrolled syntheses of biotin-labeled oligosaccharide portions containing the carbohydrate moiety of glycoprotein from Echinococcus granulosus have been accomplished. Trisaccharide Galβ1-3Galβ1-3GalNAcα1-R ( A ), tetrasaccharide Galα1-4Galβ1-3Galβ1-3GalNAcα1-R ( B ), and pentasaccharide Galα1-4Galβ1-3Galβ1-3Galβ1-3GalNAcα1-R ( C ), (R = biotinylated probe) were synthesized by stepwise condensation and/or block synthesis by the use of 5-(methoxycarbonyl)pentyl 2-azido-4,6- O -benzylidene-2-deoxy-α-d-galactopyranoside as a common glycosyl acceptor. The synthesis of the tetrasaccharide and the pentasaccharide was improved from the viewpoint of reducing the number of synthetic steps and increasing the total yield by changing from stepwise condensation to block synthesis. Moreover, hexasaccharide E , which contains the oligosaccharide sequence which occurs in E. granulosus , was synthesized from trisaccharide D . We examined the antigenicity of these five oligosaccharides by an enzyme-linked immunosorbent assay (ELISA). Although compounds of C - E did not exhibit antigenicity against cystic echinococcosis (CE) patient sera, compounds B , D , and E showed good serodiagnostic potential for alveolar echinococcosis (AE).

A Kampo prescription usually consists of several crude drugs and contains many kinds of compounds. Physicochemical interactions between the compounds may occur in the process of decoction, by which Kampo prescriptions are usually prepared for ingestion, and the interactions may change the extraction yields of the constituents. Berberine and baicalin have been reported to form precipitates. Orengedokuto, which consist of Coptis Rhizome, Gardenia Fruit, Phellodendron Bark and Scutellaria Root, has been a representative Kampo prescription used to treat inflammatory diseases. In our previous papers, we revealed that the precipitates formed in the decoction of orengedokuto without Gardenia Fruit mainly consists of berberine-baicalin complex and that Gardenia Fruit reduced the amount of the precipitates in orengedokuto decoction. In this report, through solubility-enhancement assay based on HPLC, we identified crocins as the constituents of Gardenia Fruits, which enhanced the solubility of berberine-baicalin complex. All-trans crocin-1 (1) and 13-cis crocin-1 (5) showed high activities among the isolated crocins, and the number of glucosyl groups in the molecule seemed correlated with the activity. As berberine and baicalin were reported as the anti-inflammatory constituents of Coptis Rhizome and Phellodendron Bark, and Scutellaria Root, respectively, Gardenia Fruit contributes anti-inflammatory activity of orengedokuto by increasing solubilities of anti-inflammatory constituents of the other component crude drugs in the prescription. Our result will add a scientific basis to the understanding of the effectiveness of orengedokuto as a whole.