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The dichloromethane extract of the roots of Bridelia balansae Tutcher (Phyllanthaceae) was found to show potential anticancer activity against HCT116 colorectal cancer cell. Our bioassay-guided phytochemical investigation of the roots of B. balansae led to the identification of 14 compounds including seven lignans ( 1 - 7 ), three phenylbenzene derivatives ( 8 - 10 ), two flavanone ( 11 - 12 ), and two triterpenoids ( 13 - 14 ). Among them, 4'-demethyl-4-deoxypodophyllotoxin ( 1 ) is the first aryltetralin lignan compound identified from this plant species. In addition, the stereochemistry of 1 was validated by X-ray crystallography for the first time, and its distinguished cytotoxic effect on HCT116 cells with an IC 50 value at 20 nM was induced via an apoptosis induction mechanism. Compound 1 could also significantly decrease the migration rate of HCT116 cells, indicating its potential application against cancer metastasis. The western blot analysis showed that 1 has the potential to inhibit cell proliferation and metastasis. Treatment of 1 resulted in the downregulation of matrix metalloproteinases 2 (MMP2) and p-Akt, while p21 was upregulated. Collectively, the present study on the phytochemical and biological profile of B. balansae has determined the plant as a useful source to produce promising anticancer lead compounds.

Introduction: The plant Patrinia villosa Juss. (PV) has long been used as a medicinal herb for treating intestinal disorders. Pharmacological activities such as anti-oxidation, anti-inflammation, and anti-cancer effects of compounds isolated from PV have been reported, but these bioactive compounds were not derived from PV water extract (PVW). Therefore, in the present study, we aimed to identify the active component(s) of PVW which exhibit inhibitory activities in colon cancer cells viability and migration. Methods: Human colon cancer HCT116 cells were treated with the isolated compounds of PVW and then subjected to MTT and transwell migration assays. Results: Our results showed that an active compound in PVW, 8,9-didehydro-7-hydroxydolichodial (DHD) inhibited cell viability of HCT116 cells, with IC 50 value at 6.1 ± 2.2 μM. Interestingly, DHD was not detected in the herbal material of PV. Further investigation revealed that DHD is in fact a heat-generated compound derived from a natural compound present in PV, namely valerosidate. Valerosidate also reduced cell viability in HCT116 cells, with IC 50 value at 22.2 ± 1.1 μM. Moreover, both DHD (2.75 μM) and valerosidate (10.81 μM) suppressed cell migration in HCT116 cells, with inhibitory rates at 74.8% and 74.6%, respectively. In addition, western blot results showed that DHD (5.5 μM) could significantly increase p53 expression by 34.8% and PTEN expression by 13.9%, while valerosidate (21.6 μM) could increase expressions of p53 and PTEN by 26.1% and 34.6%, respectively in HCT116 cells after 48 h treatment. Discussion: Taken together, this is the first report that a naturally-occurring valerosidate present in PV could actually transform to DHD by thermal hydrolysis, and both compounds exhibited inhibitory effects on cell viability and migration in HCT116 cells via increasing the expressions of tumor suppressors (p53 and PTEN). Our findings demonstrated that valerosidate is present in raw herb PV but not in PVW, while DHD is present in PVW rather than in raw herb PV. This difference in chemical profiles of raw herb and boiled water extract of PV may affect the anti-cancer activity, and hence further investigations are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Zheng, Ku, Ngai, Yue, Lee and Lau.)

A new icetexane diterpenoid, 11, 12, 20α-trihydroxyl-7β-methoxyicetexa-8, 11, 13-triene-19, 10-lactone [Phyllane A ( 1 )], and a new abietane diterpenoid, 7β, 20-epoxy-3β, 17-acetoxy-abieta-8, 11, 13-teriene-11, 12-diol [phyllane B ( 2 )], along with two known compounds ( 3 and 4 ) were isolated from the methanol (MeOH) extract of twigs and leaves of the folk medicinal Isodon phyllopodus . Their structures were determined by spectroscopic analyses including 2 D NMR spectral data, and further confirmed by X-ray single crystal diffraction. Moreover, the compounds were evaluated for their cytotoxicity and anti-HIV activities, and phyllane A showed anti-HIV activity with an IC 50 value of 15.7 μM, but phyllane B was found to be cytotoxic to the A549 host cells with a CC 50 value of 108.5 μM.

Arylnaphthalene lignans (ANLs) were known to have axial chirality due to the biphenyl skeleton with hindered rotation at the single bond. However, the stable ANL atropisomers have not been isolated from nature until the present study. Phytochemical separation of the methanol extract of the stems and barks of Justicia procumbens led to the isolation of 11 ANL glycosides including four pairs of new atropisomers with stable confirmations at room temperature. Their structures were deduced from elucidation of the extensive spectral data, and their absolute configurations were determined by the circular dichroism, electronic circular dichroism, and X-ray methods as well as the total synthesis of one pair of the atropisomers. The ANL compounds were evaluated for their antiviral potential, and it was found that they displayed great antiviral activity discrepancy between a pair of atropisomers due to the geometric orientation. The 1' P -oriented atropisomers showed much more significant antiviral potency than their corresponding 1' M -oriented counterparts. The biological activity discrepancy caused by the axial chirality will not only inspire synthetic design of novel ANL atropisomers to enrich the structural diversity, but also provide important hints to direct the synthetic approaches toward the antiviral drug development of ANL compounds.

In the course of our ongoing studies to discover bioactive chemical constituents from plants in the genus Isodon, two new diterpenes, kunminolide A (1) and rabdokunmin F (2) were isolated from the leaves of the medicinal plant Isodon interruptus. Kunminolide A (1) is a novel abietane-like diterpene with a novel skeleton, herein designated as 9, 10-seco-neoabietane. Rabdokunmin F (2) is an ent-kaurene diterpene with C-18 oxidized to a carboxylic acid group. The structures were determined by spectroscopic means including analysis of 1D- and 2D-NMR spectral data. Crystals of 1 obtained from methanol were suitable for X-ray analysis, which confirmed the chemical structure. Kunminolide A (1) demonstrated chemopreventive potential by inducing QR1 activity with a CD value of 14.3 µM, and rabdokunmin F (2) was found to have cytotoxic activities with IC 50 values in the range of 1.1-3.0 µM., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Twenty-one lignans including three new ones (1, 2 and 13) were isolated from Justicia procumbens. The chemical structures of the new lignans were determined by spectroscopic means including 1D and 2D NMR analysis. These compounds were evaluated for their cytotoxic and anti-HIV activities. The new secoisolariciresinol dimethyl ether acetate (13) exhibited anti-HIV-1 activity with an IC 50 value of 5.27 μmol·L -1 and a selective index (SI) value of 2.2. The known arylnaphthalene lignan procumbenoside A (3) and diphyllin (8) demonstrated inhibitory activity against HIV-1 with IC 50 values of 4.95 (SI > 6.2) and 0.38 μmol·L -1 (SI = 5.3), respectively., (Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Javanicunines A-B and 9-deoxy-PF1233s A-B belong to a family of natural diketomorpholines with a unique isopropenyl group at C-10b or C-5a and a hydroxyl group at C-11a or C-10b. We herein reported the first total synthesis of javanicunines A-B and 9-deoxy-PF1233s A-B. Pivotal features of the synthesis included a nucleophilic substitution reaction, followed by a Davis' oxaziridine oxidation to assemble javanicunines A-B, and a chemoselective and stereoselective oxidation with Murray's reagent to install the requisite C-10b hydroxyl group in 9-deoxy-PF1233s A-B. The present synthesis also established the absolute configuration of javanicunine B.

We report the isolation of a novel diterpene, designated as `amethane', from Isodon amethystoides (Lamiaceae). The diterpene [amethinol A; systematic name: (4aR,4bR,7R,10aS)-4b,7-dihydroxy-7-isopropyl-1,1-dimethyl-9-oxododecahydrobenzo[a]azulene-4a(2H)-carboxylic acid], possesses a unique skeleton containing a six/five/seven-membered tricyclic system. Intermolecular O-H...O close contacts were found to the carboxyl, carbonyl and hydroxy groups, connecting molecules into a two-dimensional structure. A possible biosynthetic pathway has been proposed. In addition, the compound was evaluated for its biological activities against different disease targets, and was found to significantly attenuate RORγt-dependent autoimmune responses.

Concise total syntheses of the natural phytoalexins 2-hydroxy-8-(4-hydroxyphenyl)phenalen-1-one (1), 2-hydroxy-8-(3,4-dihydroxyphenyl)phenalen-1-one (2), and hydroxyanigorufone (4), together with regioisomer 3 are accomplished in 11 or 12 steps. The synthetic strategy features a Friedel-Crafts acylation to construct the 1H-phenalen-1-one tricyclic core followed by a Suzuki cross-coupling to obtain the target compounds.

The stems of Dendrobium orchids (Orchidaceae), also known as Shi Hu, have been used for medicinal purposes for centuries in oriental countries. In fact, the health benefits of Shi Hu have been evidenced by its modern pharmacological actions on conquering oxidative stress in pathological conditions. From the extracts of two commonly used Dendrobium species, we obtained discernible amounts of stilbenoids, explicitly trans-resveratrol (1) and dihydro-resveratrol (2), which are prototypical antioxidants. When applied to cultured melanocytes, these stilbenoids, dihydro-resveratrol (2) in particular, significantly reduced melanin formation via inhibiting tyrosinase activity and expression of tyrosinase-related proteins. By utilizing dihydro-resveratrol (2) as the basic structural unit, we synthesized 11 novel dihydrostilbene derivatives (3-13) in good yields and purity, with manipulative steps. In addition to their anti-melanogenic activity, some of the novel derivatives are indeed potential antioxidants as they quenched intracellular oxidative radicals in a manner more efficient than Trolox, a water-soluble analogue of vitamin E, and thus premeditated beneficial to skin protection., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Acori Tatarinowii Rhizoma (ATR; rhizome of Acorus tatarinowii Schott) ( Shi Chang Pu ) is widely used in Chinese medicine (CM) to resuscitate, calm the mind, resolve shi ( dampness ) and harmonize the wei ( stomach ). Seven different species have been identified as belonging to the genus Acorus , all of which can be found in China. However, it can be difficult to distinguish the different species of Acorus because of their morphological similarities. The aim of this study was to authenticate Acorus species using macroscopic and microscopic techniques, chemical analysis and DNA authentication and to compare the resolution power and reliability of these different methods., Methods: Four batches of ATR, Acori Graminei Rhizoma (AGR), Acori Calami Rhizoma (ACR) and Anemones Altaicae Rhizoma (AAR) (totaling 16 samples) were collected from Hong Kong and mainland China. The major characteristic features of these Acorus species were identified by macroscopic and microscopic examination. The identified samples were also analyzed by UHPLC analysis. Principal component analysis (PCA) and hierarchal clustering analysis (HCA) on UHPLC results were used to differentiate between the samples. An internal transcribed spacer (ITS) was selected as a molecular probe and a modified DNA extraction method was developed to obtain trace amounts of DNA from the different Acorus species. All extracted DNA sequences were edited by Bioedit and aligned with the ClustalW. And the sequence distances were calculated using the Maximum Parsimony method., Results: Macroscopic and microscopic analyses allowed for AAR to be readily distinguished from ATR, AGR and ACR. However, it was difficult to distinguish between ATR, AGR and ACR because of their similar morphological features. Chemical profiling revealed that α- and β-asarone were only found in the ATR, AGR and ACR samples, but not in the AAR samples. Furthermore, PCA and HCA allowed for the differentiation of these three species based on their asarone contents. Morphological authentication and chemical profiling allowed for the partial differentiation of ATR, AGR ACR and AAR. DNA analysis was the only method capable of accurately differentiating between all four species., Conclusion: DNA authentication exhibited higher resolution power and reliability than conventional morphological identification and UHPLC in differentiating between different Acorus species.

Acute pancreatitis is an inflammatory process originated in the pancreas; however, it often leads to systemic complications that affect distant organs. Acute respiratory distress syndrome is indeed the predominant cause of death in patients with severe acute pancreatitis. In this study, we aimed to delineate the ameliorative effect of dihydro-resveratrol, a prominent analog of trans-resveratrol, against acute pancreatitis-associated lung injury and the underlying molecular actions. Acute pancreatitis was induced in rats with repetitive injections of cerulein (50 µg/kg/h) and a shot of lipopolysaccharide (7.5 mg/kg). By means of histological examination and biochemical assays, the severity of lung injury was assessed in the aspects of tissue damages, myeloperoxidase activity, and levels of pro-inflammatory cytokines. When treated with dihydro-resveratrol, pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening were significantly reduced in rats with acute pancreatitis. In addition, the production of pro-inflammatory cytokines and the activity of myeloperoxidase in pulmonary tissues were notably repressed. Importantly, nuclear factor-kappaB (NF-κB) activation was attenuated. This study is the first to report the oral administration of dihydro-resveratrol ameliorated acute pancreatitis-associated lung injury via an inhibitory modulation of pro-inflammatory response, which was associated with a suppression of the NF-κB signaling pathway., (Copyright © 2016 John Wiley & Sons, Ltd.)

Cordyceps sinensis is an endoparasitic fungus widely used as a tonic and medicinal food in the practice of traditional Chinese medicine (TCM). In historical usage, Cordyceps specifically is referring to the species of C. sinensis. However, a number of closely related species are named themselves as Cordyceps, and they are sold commonly as C. sinensis. The substitutes and adulterants of C. sinensis are often introduced either intentionally or accidentally in the herbal market, which seriously affects the therapeutic effects or even leads to life-threatening poisoning. Here, we aim to identify Cordyceps by DNA sequencing technology. Two different DNA-based approaches were compared. The internal transcribed spacer (ITS) sequences and the random amplified polymorphic DNA (RAPD)-sequence characterized amplified region (SCAR) were developed here to authenticate different species of Cordyceps. Both approaches generally enabled discrimination of C. sinensis from others. The application of the two methods, supporting each other, increases the security of identification. For better reproducibility and faster analysis, the SCAR markers derived from the RAPD results provide a new method for quick authentication of Cordyceps.

Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2).

Cutaneous melanoma is the most life-threatening neoplasm of the skin, accounting for most of the skin cancer deaths. Accumulating evidence suggests that targeting metabolism is an appealing strategy for melanoma therapy. Mitochondrial NAD(P)(+)-dependent malic enzyme (ME2), an oxidative decarboxylase, was evaluated for its biological significance in cutaneous melanoma progression. ME2 mRNA and protein expression significantly increased during melanoma progression, as evidenced by Gene Expression Omnibus analysis and immunohistochemistry on clinically annotated tissue microarrays, respectively. In addition, ME2 knockdown attenuated melanoma cell proliferation in vitro. ME2 ablation resulted in reduced cellular ATP levels and elevated cellular reactive oxygen species production, which activated the AMP-activated protein kinase pathway and inhibited acetyl-CoA carboxylase. Furthermore, ME2 expression was associated with cell migration and invasion. ME2 knockdown decreased anchorage-independent growth in vitro and tumor cell growth in vivo. These results suggested that ME2 might be an important factor in melanoma progression and a novel biomarker of invasion.

Hepatoma upregulated protein (HURP) is originally isolated during the search for the genes associated with hepatoma. HURP is upregulated in many human cancers. Culture cells exhibit transformed and invasive phenotype when ectopic HURP is introduced, revealing HURP as an oncogene candidate. Our previous studies demonstrated that Aurora-A regulated the cell transforming activities of HURP by phosphorylating HURP at four serines. To unravel how the Aurora-A/HURP cascade contributes to cell transformation, we firstly noticed that HURP shuttled between cytoplasm and nucleus. The nuclear localization activity of HURP was promoted or abolished by overexpression or knockdown of Aurora-A. Similarly, the HURP phosphorylation mimicking mutant 4E had higher nuclear targeting activity than the phosphorylation deficient mutant 4A. The HURP 4E accelerated G1 progression and upregulated cyclin E1, and the cyclin E1 upregulating and cell transforming activities of HURP were diminished when the nuclear localization signal (NLS) was removed from HURP. Furthermore, HURP employed p38/nuclear factor-κB (NF-κB) cascade to stimulate cell growth. Interestingly, NF-κB trapped HURP in nucleus by interacting with HURP 4E. At last, the HURP/NF-κB complex activated the cyclin E1 promoter. Collectively, Aurora-A/HURP relays cell transforming signal to NF-κB, and the HURP/NF-κB complex is engaged in the regulation of cyclin E1 expression., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Cells display dramatic morphological changes in mitosis, where numerous factors form regulatory networks to orchestrate the complicated process, resulting in extreme fidelity of the segregation of duplicated chromosomes into two daughter cells. Astrin regulates several aspects of mitosis, such as maintaining the cohesion of sister chromatids by inactivating Separase and stabilizing spindle, aligning and segregating chromosomes, and silencing spindle assembly checkpoint by interacting with Src kinase-associated phosphoprotein (SKAP) and cytoplasmic linker-associated protein-1α (CLASP-1α). To understand how Astrin is regulated in mitosis, we report here that Astrin acts as a mitotic phosphoprotein, and Aurora-A phosphorylates Astrin at Ser(115). The phosphorylation-deficient mutant Astrin S115A abnormally activates spindle assembly checkpoint and delays mitosis progression, decreases spindle stability, and induces chromosome misalignment. Mechanistic analyses reveal that Astrin phosphorylation mimicking mutant S115D, instead of S115A, binds and induces ubiquitination and degradation of securin, which sequentially activates Separase, an enzyme required for the separation of sister chromatids. Moreover, S115A fails to bind mitosis regulators, including SKAP and CLASP-1α, which results in the mitotic defects observed in Astrin S115A-transfected cells. In conclusion, Aurora-A phosphorylates Astrin and guides the binding of Astrin to its cellular partners, which ensures proper progression of mitosis., (Copyright © 2014 the American Physiological Society.)

Aims and Objectives: The aim of this study was to investigate the association between distress symptoms and the types of complementary and alternative medicine use in patients with cancer., Background: Patients diagnosed with cancer have increasingly turned to the use of complementary and alternative medicine to manage its symptoms and cope with the side effects of conventional treatment., Design: A descriptive cross-sectional study., Methods: A face-to-face interview using a structured questionnaire was conducted with 208 outpatients at a medical centre in central Taiwan. The questionnaire included questions on socio-demographic information, disease specifics, distress symptoms and complementary and alternative medicine usage in the past 12 months. Logistic regression analysis was used to assess the association between distress symptoms and the use of different complementary and alternative medicine modalities., Results: A total of 165 (79·3%) patients reported use of at least one complementary and alternative medicine modality during the past 12 months. Complementary and alternative medicine users and non-users were not significantly different in age, sex, marital status, education level, religious affiliation and disease-related variables. Fatigue (66·8%) was the most frequently reported symptoms and was significantly associated with complementary and alternative medicine use (OR = 14·11, p = 0·001). Regarding specific complementary and alternative medicine modalities, chanting and enzyme therapy were found to be associated with 13 (68·4%) of the 19 distress symptoms., Conclusions: There was no association between complementary and alternative medicine use and demographic or disease-related variables. Complementary and alternative medicine was widely used by patients with cancer, and symptom of fatigue was most strongly associated with complementary and alternative medicine use. Chanting and enzyme therapy were the two most frequently used complementary and alternative medicine modalities that were significantly associated with the 19 distress symptoms., Relevance to Clinical Practice: Health care providers should ask their patients about their complementary and alternative medicine use to avoid possible adverse interactions between conventional treatment and complementary and alternative medicine interventions, in particular, those remedies that are likely to interact with cancer medications., (© 2011 Blackwell Publishing Ltd.)

Background: Total thyroidectomy is increasingly being adopted for patients requiring surgical treatment for Graves' disease based on a comparable surgical risk and the lack of recurrence, as well as the questionable ability of subtotal thyroidectomy to maintain euthyroidism. The purpose of the present paper was to evaluate its safety and efficiency., Methods: Total thyroidectomy was adopted as part of the routine surgical treatment for Graves' disease from 2000. Patients who underwent subtotal thyroidectomy (STT) from 1995 to 1999 (n = 119) were compared with those who underwent total thyroidectomy (TT) from 2000 to 2003 (n = 98) with respect to immediate postoperative morbidity and long-term outcome., Results: Fourteen (11.8%) and 22 patients (22.4%) required calcium supplement on discharge in the STT and TT groups, respectively (P < 0.05). One (0.8%) and three patients (3.1%) developed permanent hypocalcaemia, respectively. Transient recurrent laryngeal nerve palsy occurred in 9.2% (n = 11) and 5.1% (n = 5) of patients or 5.0% and 2.6% of nerves at risk after STT and TT, respectively. None of the patients had permanent nerve palsy. The estimated blood loss was less and hospital stay shorter after TT. During a mean follow up of 64 months, 86 patients (72.3%) in the STT group required thyroxine replacement and seven patients (5.9%) developed relapse., Conclusion: Subtotal thyroidectomy was associated with relapse as well as hypothyroidism in a significant proportion of patients during long-term follow up. Total thyroidectomy can be performed as safely as STT and should be recommended as the procedure of choice for patients requiring surgical treatment for Graves' disease.

We report the first case of successful surgical resection of a malignant phaeochromocytoma with tumour extension into vena cava and right atrium in a patient with multiple endocrine neoplasia type 2A. A 21-year-old woman with genetic confirmation of multiple endocrine neoplasia type 2A syndrome was diagnosed with a very rare case of malignant phaeochromocytoma with tumour thrombus extension into vena cava and right atrium causing Budd-Chiari syndrome. It posed a challenge to the surgeons with regard to complete tumour resection and vascular control. Reviewing the limited literature, surgical resection by means of cardiopulmonary bypass with hypothermic circulatory arrest has been reported with success in phaeochromocytoma with advance vascular involvement. Adopting this approach, adrenalectomy with complete thrombus excision by inferior vena cava exploration and right atriotomy were performed successfully by a multidisciplinary team.

Background: Abdominal tuberculosis is an uncommon extra-pulmonary manifestation of tuberculosis., Methods: Case report and literature review., Results: Herein, we report an unusual case of ruptured tuberculous mesenteric cold abscess, which was managed by laparotomy for diagnosis and drainage, and post-operative chemotherapy., Conclusions: Peritoneal tuberculosis may present to surgeons as ascites, an abdominal mass, or peritonitis. Preoperative diagnosis of abdominal tuberculosis is notoriously difficult. Acute peritonitis provoked by rupture of tuberculosis mesenteric cold abscess is exceedingly rare. Surgical intervention is warranted for diagnosis and drainage.