Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound

Oral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficiently expands CTC from patients to test Antrodia Cinnamomea mycelium-derived bioactive compounds. Three ACM-derived bioactive compounds were evaluated for tumor chemosensitization characteristics. Significant and consistent cytotoxic/5-FU sensitizing effects of GKB202 were found on 8 different patient-derived tumors. Acute toxicity profile and hepatic metabolism of GKB202 in rats suggest GKB202 is rapidly cleared by liver and is well tolerated up to the dose of 20 mg/kg. This comprehensive study provides new evidence that liquid fermentation of Antrodia cinnamomea mycelium (ACM) contains bioactive compounds that lead to effective control of CTC, especially when combined with 5-FU. Together, these data suggest ACM-derived GKB202 may be considered for further clinical investigation in the context of 5-FU-based combination therapy.     

Bioactive Components from the Mycelium of Antrodia Salmonea

Three new compounds, 2,4‐dimethoxy‐6‐methylbenzene‐1,3‐diol ( 1 ), salmoquinone ( 2 ), and 3‐(4‐hydroxyphenyl)‐4‐isobutyl‐1H‐pyrrole‐2,5‐dione ( 3 ), together with six known compounds, 2‐methoxy‐6‐methyl‐p‐benzoquinone ( 4 ), 2,3‐dimethoxy‐5‐methyl‐p‐benzoquinone ( 5 ), 2‐hydroxy‐5‐methoxy‐3‐methyl‐p‐benzoquinone ( 6 ), eburcoic acid ( 7 ), fomefficinic acid C ( 8 ), and a pyrroledione ( 9 ), were isolated from the mycelium of Antrodia salmonea. The structures of these compounds were elucidated by spectrometric analyses including IR, NMR, and MS. Among these compounds, 4 and 5 exhibited cytotoxicity against KB, HepG2, and H2058 cell lines.     

The Chemical Constituents of Polypodium Niponicum

Three new steroids named as shuilongguine I ( 1 ), shuilongguine II ( 2 ) and shuilongguine III ( 3 ), together with eleven known compounds were isolated from Polypodium niponicum (Chinese name “Shuilonggu”, Berberidaceae). Their structures were deduced by spectroscopic methods and 2D NMR experiments.     

Constituents of Clinopodium Umbrosum

The isolation and identification of fifteen crystalline components from the whole herb of Clinopodium umbrosum (Bieb.) C. Koch (Labiatae) are described. Their structures were determined on the basis of spectral evidence and chemical transformation. These compounds include five steroids (α-spinasterone, β-sitosterol, stigmasterol, α-spinasterol, and α-spinasteryl-3-O-β-glucopyranoside), four triterpenoids (3β-hydroxyurs-11-en-28,13-olide, betulinic acid, oleanolic acid, ursolic acid), four flavonoids (luteolin, luteolin-7-O-β-glucopyranoside, apigenin-7-O-β-glucuronide, and apigenin-7-O-β-methylglucuronate), and two lignolic acids [3-(3,4-dihydroxyphenyl)- lactic acid and rosmarinic acid].     

Cyclodextrin‐modified capillary electrophoresis for achiral and chiral separation of ergostane and lanostane compounds extracted from the fruiting body of Antrodia camphorata

A CD‐modified capillary electrophoretic method has been developed for achiral and chiral analysis of seven bioactive compounds isolated from the fruiting body of Antrodia camphorata. Such important target analytes exhibit similar chemical structures and are known for their diverse properties including antioxidant and anticancer effects. The analytes were separated in 25 min using a pH 9.3, 20 mM sodium borate buffer containing 20 mM methyl‐β‐CD and 30 mM sulfobutylether‐β‐CD. With the exception of the optical isomer pairs (antcin B or zhankuic acid A, zhankuic acid C, and antcin A), the remaining bioactive compounds including the chiral pair antcin C were baseline‐separated. Analysis time was noticeably longer to baseline separate all of the above chiral pairs (～38 min) by adding 5% DMF to the running buffer. The migration order was reversed compared with the HPLC elution. More hydrophobic compounds complexed favorably with methyl‐β‐CD and emerged earlier in the electropherogram than their more hydrophilic counterparts which were strongly associated with sulfobutylether‐β‐CD. The simple capillary electrophoretic method developed was applicable for rapid separation and characterization of several important bioactive compounds isolated from the fruiting body of A. camphorata.     

Constituents of the Heartwood of Diospyros Eriantha

The isolation and identification of fifteen compounds from the heartwood of Diospyros eriantha are described. Their structures were determined on the basis of spectral evidence and/or comparison with authentic samples. These compounds include three steroids (stigmast-4-en-3-one, stigmast-4-ene-3,6-dione, and 3β-hydroxystigmast-5-en-7-one), seven triterpenoids (friedelin, lupeol, betulinaldehyde, 3β-acetoxyurs-11-en-13,28-olide, 3β-acetoxyoleanolic acid, betulin, and betulinic acid), three quinones (2-ethoxy-7-methyljuglone, 3-ethoxy-7-methyljuglone, and 2,6-dimethoxy-1,4-benzoquinone), and two phenols (3,4,5-trimethoxyphenol, and syringic acid).     

川桂皮挥发油的化学组成

采用GC－MS技术分析了川桂（Cinnamomum wilsonii）皮挥发油的化学组成，共确定了其中42种化学成分与相对含量，占总组分相对含量的94．14％，其中有40种为萜类或其衍生物；研究结果显示，川桂皮油的主要成分为桉油素（11．02％），1（10），4－杜松二烯（10．21％），乙酸异龙脑酯（6．30％），杜松醇（5．53％），桉叶油醇（5．34％）等，与该植物叶和同属药用植物肉桂皮挥发油的主要组成均差别较大。     

Chemical Constituents of Heartwood of Bauhinia purpurea

The isolation and identification of twenty-two components from the heartwood of Bauhinia purpurea are described. Their structures were determined on the basis of spectral evidence as well as direct comparison with authentic samples. Those components included six steroids, two triterpenoids, three fatty alcohol, acid and ester, two glycerols, five flavonoids, two phenols, one chromone, and one sugar. Among these, 6′-(β-sitosteryl-3-O-β-glucopyranosidyl)tetraeicosanoate is a new compound.     

Constituents of the Whole Herb of Clinoponium laxiflorum

The isolation and identification of twenty‐two components (including one new compound) from the whole herb of Clinoponium laxiflorum (Hay) Matsum (Labiatae) are described. Their structures were determined on the basis of spectral and chemical transformation. One new compound is methyl rosmarinate. The other twenty‐one compounds include three steroids (α‐spinasterol, α‐spinasteryl‐3‐O‐β‐D‐glucopyranoside, and β‐sitosteryl‐3‐O‐β‐glucopyranoside), three triterpenes (oleanolic acid, ursolic acid, and betulinic acid), nine flavonoids (didymin, apigenin‐7‐O‐β‐glucopyranoside, luteolin‐7‐O‐β‐glucopyranoside, isosakuranetin, narigenin, apigenin, luteolin, narirutin, and hesperidin), three lignolic acids (rosmarinic acid, 3‐(3,4‐dihydroxyphenyl)lactic acid, and caffeic acid), and three phenols (4‐hydroxybenzaldehyde, 3,4‐dihydroxybenzaldehyde, and 3,4‐dihydroxybenzoic acid).     

Chemical Constituents from the Leaves of Zanthoxylum Schinifolium

cis‐Fagaramide ( 1 ), a new amide, together with fifty known compounds, have been isolated from the leaves of Zanthoxylum schinifolium. These known compounds include twenty‐one coumarins, eleven alkaloids, one furan, four benzenoids, three chlorophylls, four triterpenoids, one diterpenoid, one sesquiterpenoid, and four steroids. The structures of these compounds were determined by means of spectral analyses.     

Studies on the Constituents from the Bark of Bauhinia Purpurea

In a previous paper, were ported a new stigmasteroyl glucoside derivative together with four known compounds. In addition to the above compounds, the isolation and identification of twenty‐four compounds from the same source are described here. Their structures were deter mined on the basis of spectral evidence as well as comparison with authentic samples. Those compounds included four waxes, four triterpenes, eight steroids, two glyceride, three flavonoids, and three phenylpropanoids. Some new compounds were found in mixtures of three alkyl ω‐hydroxyalkanoate, glyceride, and phenylpropanoids.     

Impedance Analysis of Single Melanoma Cells in Microfluidic Devices

The electrical impedance analysis of single cells can provide information on cells’ pathological condition in various environments. Cell electrical properties are affected by factors such as the location, adhesion, and size of the cell. The proposed microfluidic device captures a single cell, maintains growth conditions, and allows single‐melanoma‐cell impedance to be measured using an impedance analyzer and a function generator. The rate of impedance variation (ROIV) can be used to determine cell growth conditions. Cellular apoptosis affects cell size and membrane surface area, and thus the electrical properties of cells. At 24 h without Antrodia cinnamomea (AC) addition, ROIV was 15.23 %, 17.04 %, and 12.60 % at temperatures of 34 °C, 37 °C, and 40 °C, respectively. At 24 h and 37 °C, ROIV was 17.04 %, 40.37 %, and 45.02 % for AC concentrations of 0, 20, and 40 µL/mL, respectively. The results show that the cell impedance variation of cells cultured without AC is much lower than that of cells cultured with AC. Regarding cellular morphology, with AC addition, the cells shrank obviously after 24 h, whereas they barely shrank without AC addition.     

肉桂挥发油的超临界CO2萃取法与水蒸气蒸馏法提取的比较分析

采用超临界CO2萃取法与水蒸气蒸馏法从肉桂中提取挥发油,用GC-MS法测定其化学成分和相对含量,对两种提取方法所得的挥发油进行比较,水蒸气蒸馏提取肉桂挥发油的产率为1％(ω),主要成分为肉桂醛、α-芹子烯、α-（王古）Ba烯、δ-杜松烯;超临界CO2萃取法提取的产率为1．5％(W),主要成分为肉桂醛、α-玷圯烯、α-依兰油烯、δ-杜松烯等。     

The Synthesis of a Novel Lignan

Lignans have attracted much interest over the years on account of their widespread ocurrence in nature1, and on account of their broad range of biological activity2. Thus, several lignans are known to exhibit anti-tumor activity3-7, while others function as growth inhibitors and antifungal agents8,9. The importance is the isolation of lignans from animals, including human beings10-12, which has led to the suggestion that such compounds may be an example of a novel class of hormone controlling …     

A new lignan derivative from the root of Ilex pubescens

One new compound, ilexlignan A （1）, was isolated from the root of llex pubescens. Its structure was elucidated by the combination of one- and two-dimensional NMR analysis, mass spectrometry, CD spectrum measurement and chemical evidence.     

An efficient method for the synthesis of lignans

An efficient approach for the synthesis of several types of lignans (dibenzylbutanediols, dibenzylbutanes, substituted tetrahydrofurans, aryldihydronaphthalenes, arylnaphthalenes, and aryltetralins) was developed. The regioselective oxidative coupling of ethyl ferulate was used as the key step.     

The Facile Reversed‐Phase HPLC Resolution of Tetrahydrofurofuran Nucleus Lignans in Traditional Chinese Medicine: Quantitative Analysis of Asarinin and Sesamin in Asari Radix

Eight tetrahydrofurofuran nucleus lignans: syringaresinol, epi‐syringaresinol, lirioresinol‐B dimethyl ether, xanthoxylol, phillygenin, fargesin, sesamin and asarinin are separated on a C₁₈ column in the reversed‐phase mode. These lignans are plant products formed primarily by the carbon‐carbon coupling of derivatives of cinnamyl alcohol units, in which the two units may be linked by an oxygen bridge to form a tetrahydrofurofuran nucleus and are found to be highly similar in structure. However, these lignans can be baseline resolved under gradient elution in less than 25 minutes. The resolution also can be optimized through altering the flow rate in an isocratic elution. This method is proven to be facile and reliable in routine quantitative analysis of ingredients such as asarinin and sesamin in traditional Chinese medicine Asarum sieboldii. The corresponding recoveries (%) were found to be 95.65 and 96.14, respectively.     

The total synthesis of sevanol,a novel lignan isolated from the thyme plant (Thymus armeniacus)

Recently, a novel lignan sevanol was isolated from the thyme plant Thymus armeniacus. During structure-functional elucidation it showed significant biological activity on ASIC3 acid sensing channels. Herein we describe the first synthesis of sevanol with a 3% overall yield. The construction of a dihydronaphthalene ring by oxidative dimerization of a protected dihydroxycinnamic acid ester in the presence of ferric chloride (III) is a key step in this first total synthesis of sevanol.     

Taiwanin H,A New Lignan from the Barks of Taiwania Cryptomerioides Hayata

A new lignan, taiwanin H, has been isolated from the barks of Taiwania cryptomerioides Hayata and elucidated as formula ( 6a ) by chemical and physical evidence.