Artemisia argyi extracts overcome lapatinib resistance via enhancing TMPRSS2 activation in HER2-positive breast cancer.

Breast cancer stands as the predominant malignancy and primary cause of cancer-related mortality among females globally. Approximately 25% of breast cancers exhibit HER2 overexpression, imparting a more aggressive tumor phenotype and correlating with poor prognoses. Patients with metastatic breast cancer receiving HER2 tyrosine kinase inhibitors (HER2 TKIs), such as Lapatinib, develop acquired resistance within a year, posing a critical challenge in managing this disease. Here, we explore the potential of Artemisia argyi, a Chinese herbal medicine known for its anti-cancer properties, in mitigating HER2 TKI resistance in breast cancer. Analysis of the Cancer Genome Atlas (TCGA) revealed diminished expression of transmembrane serine protease 2 (TMPRSS2), a subfamily of membrane proteolytic enzymes, in breast cancer patients, correlating with unfavorable outcomes. Intriguingly, lapatinib-responsive patients exhibited higher TMPRSS2 expression. Our study unveiled that the compounds from Artemisia argyi, eriodictyol, and umbelliferone could inhibit the growth of lapatinib-resistant HER2-positive breast cancer cells. Mechanistically, they suppressed HER2 kinase activation by enhancing TMPRSS2 activity. Our findings propose TMPRSS2 as a critical determinant in lapatinib sensitivity, and Artemisia argyi emerges as a potential agent to overcome lapatinib via activating TMPRSS2 in HER2-positive breast cancer. This study not only unravels the molecular mechanisms driving cell death in HER2-positive breast cancer cells induced by Artemisia argyi but also lays the groundwork for developing novel inhibitors to enhance therapy outcomes.

Inhibition of Autophagy Aggravates Arachis hypogaea L. Skin Extracts-Induced Apoptosis in Cancer Cells.

The skin of Arachis hypogaea L. (peanut or groundnut) is a rich source of polyphenols, which have been shown to exhibit a wider spectrum of noteworthy biological activities, including anticancer effects. However, the anticancer activity of peanut skin extracts against melanoma and colorectal cancer (CRC) cells remains elusive. In this study, we systematically investigated the cytotoxic, antiproliferative, pro-apoptotic, and anti-migration effects of peanut skin ethanolic extract and its fractions on melanoma and CRC cells. Cell viability results showed that the ethyl acetate fraction (AHE) of peanut skin ethanolic crude extract and one of the methanolic fractions (AHE-2) from ethyl acetate extraction exhibited the highest cytotoxicity against melanoma and CRC cells but not in nonmalignant human skin fibroblasts. AHE and AHE-2 effectively modulated the cell cycle-related proteins, including the suppression of cyclin-dependent kinase 4 (CDK4), cyclin-dependent kinase 6 (CDK6), phosphorylation of Retinoblastoma (p-Rb), E2F1, Cyclin A, and activation of tumor suppressor p53, which was associated with cell cycle arrest and paralleled their antiproliferative efficacies. AHE and AHE-2 could also induce caspase-dependent apoptosis and inhibit migration activities in melanoma and CRC cells. Moreover, it is noteworthy that autophagy, manifested by microtubule-associated protein light chain 3B (LC3B) conversion and the aggregation of GFP-LC3, was detected after AHE and AHE-2 treatment and provided protective responses in cancer cells. Significantly, inhibition of autophagy enhanced AHE- and AHE-2-induced cytotoxicity and apoptosis. Together, these findings not only elucidate the anticancer potential of peanut skin extracts against melanoma and CRC cells but also provide a new insight into autophagy implicated in peanut skin extracts-induced cancer cell death.

Two new chromones and a new coumarin from the fruit of Cnidium monnieri (L.) Cusson.

Two new chromones named cnidimol G (1) and cnidimol H (2), one new coumarin, 7-methoxy-8-(3-methoxy-3-methyl-2-oxobutyl)coumarin (3), and twenty known compounds were isolated from MeOH extract of the fruit of Cnidium monnieri (L.) Cusson. The structures of compounds were elucidated by extensive spectroscopic analyses including 1 D and 2 D NMR, HRESIMS, IR and UV. Anti-inflammatory activity of the selected isolated compounds were evaluated. Compounds 1 and 8 exhibited inhibitory activities against nitric oxide production.

Neuroprotective Effects of Alpinia oxyphylla Miq against Mitochondria-Related Apoptosis by the Interactions between Upregulated p38 MAPK Signaling and Downregulated JNK Signaling in the Subacute Phase of Cerebral Ischemia-Reperfusion in Rats.

Apoptosis in the penumbra region is the major cell death mechanism occurring during ischemia-reperfusion injury's early phase. Here, we evaluated how the Alpinia oxyphylla Miq (AOM) affects mitochondria-related apoptosis 3 days after transient middle cerebral artery occlusion (MCAo) and examined the mechanisms underlying the regulation of MAPK-mediated mitochondria-related apoptotic signaling in the peri-infarct cortex in rats. The rats were administered the AOM extract intraperitoneally at doses of 0.2[Formula: see text]g/kg (AOM-0.2[Formula: see text]g), 0.4[Formula: see text]g/kg (AOM-0.4[Formula: see text]g), or 0.8[Formula: see text]g/kg (AOM-0.8[Formula: see text]g) at MCAo initiation. The AOM-0.4[Formula: see text]g and AOM-0.8[Formula: see text]g significantly ameliorated apoptotic cell death and considerably downregulated cytochrome c (cyto c) and cleaved caspase-3 immunoreactivity 3 days after reperfusion. Simultaneously, they significantly downregulated cytosolic p-JNK/JNK, cathepsin B/actin, cyto c/actin, Smac/DIABLO/actin, cleaved caspase-3/actin, and AIF/actin and mitochondrial p53/HSP60 and Bax/HSP60 fractions but upregulated cytosolic p-p38 MAPK/p38 MAPK, p-p90RSK/actin, p-Bad/Bad, p-CREB/actin, and XIAP/actin and cytosolic and mitochondrial Bcl-2/Bax and Bcl-xL/Bax fractions in the peri-infarct cortex. Pretreatment with SB203580 - a p38 MAPK inhibitor - completely abrogated the effects of AOM-0.8[Formula: see text]g on the aforementioned protein expression, whereas treatment with SP600125 - a JNK inhibitor - exerted protective effects similar to those of AOM-0.8[Formula: see text]g. Treatment with 0.4 or 0.8[Formula: see text]g/kg AOM has neuroprotective effects against mitochondria-related apoptosis by suppressing cyto c, Smac/DIABLO, and AIF release from the mitochondria to cytosol. The anti-mitochondria related apoptotic effects of the AOM extract are attributable to the interactions between upregulated p38 MAPK/p90RSK-mediated p-Bad and CREB signaling and downregulated JNK/cathepsin B-mediated Bax and p53 signaling in the peri-infarct cortex 3 days after transient MCAo.

Antioxidant Effects and Phytochemical Properties of Seven Taiwanese Cirsium Species Extracts.

In the present investigation, we compared the radical-scavenging activities and phenolic contents of seven Taiwanese Cirsium species with a spectrophotometric method. We further analyzed their phytochemical profiles with high-performance liquid chromatography-photodiode array detection (HPLC-DAD). We found that the flower part of Cirsium japonicum var. australe (CJF) showed the best radical-scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and the hypochlorite ion, for which the equivalents were 6.44 ± 0.17 mg catechin/g, 54.85 ± 0.66 mmol Trolox/g and 418.69 ± 10.52 mmol Trolox/g respectively. CJF also had the highest contents of total phenolics (5.23 ± 0.20 mg catechin/g) and phenylpropanoids (29.73 ± 0.72 mg verbascoside/g). According to the Pearson's correlation coefficient, there was a positive correlation between the total phenylpropanoid content and ABTS radical-scavenging activities (r = 0.979). The radical-scavenging activities of the phenylpropanoids are closely related to their reducing power (r = 0.986). HPLC chromatograms obtained in validated HPLC conditions confirm that they have different phytochemical profiles by which they can be distinguished. Only CJF contained silicristin (0.66 ± 0.03 mg/g) and silydianin (9.13 ± 0.30 mg/g). CJF contained the highest contents of apigenin (5.56 ± 0.09 mg/g) and diosmetin (2.82 ± 0.10 mg/g). Among the major constituents, silicristin had the best radical-scavenging activities against DPPH (71.68 ± 0.66 mg catechin/g) and ABTS (3.01 ± 0.01 mmol Trolox/g). However, diosmetin had the best reducing power and radical-scavenging activity against the hypochlorite anion (41.57 ± 1.14 mg mmol Trolox/g). Finally, we found that flavonolignans (especial silicristin and silydianin) and diosmetin acted synergistically in scavenging radicals.

Angelica sinensis extract promotes neuronal survival by enhancing p38 MAPK-mediated hippocampal neurogenesis and dendritic growth in the chronic phase of transient global cerebral ischemia in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (Oliv.) Diels (ASD), commonly known as Dang Gui, is a popular Chinese herb that has long been used to treat ischemic stroke. However, the effects of ASD in chronic cerebral ischemia and its underlying mechanisms still remain unclear. AIM OF THE STUDY: This study aimed to determine the effects of the ASD extract on hippocampal neuronal survival at 28 d after transient global cerebral ischemia (GCI) and to investigate the precise mechanisms underlying the p38 mitogen-activated protein kinase (MAPK)-related signaling pathway's involvement in hippocampal neurogenesis. MATERIALS AND METHODS: Rats underwent 25 min of four-vessel occlusion. The ASD extract was intragastrically administered at doses of 0.25 g/kg (ASD-0.25 g), 0.5 g/kg (ASD-0.5 g), 1 g/kg (ASD-1 g), 1 g/kg after dimethyl sulfoxide administration (D + ASD-1 g), or 1 g/kg after SB203580 (a p38 MAPK inhibitor) administration (SB + ASD-1 g) at 1, 3, 7, 10, 14, 17, 21, and 24 d after transient GCI. RESULTS: ASD-0.5 g, ASD-1 g, and D + ASD-1 g treatments had the following effects: upregulation of bromodeoxyuridine (BrdU) and Ki67 expression, and BrdU/neuronal nuclei (NeuN) and Ki67/nestin co-expression in the hippocampal dentate gyrus (DG); upregulation of microtubule-associated protein 2/NeuN co-expression, and NeuN and glial fibrillary acidic protein (GFAP) expression, and downregulation of tumor necrosis factor-α/GFAP co-expression in the hippocampal CA1 region; upregulation of phospho-p38 MAPK (p-p38 MAPK), phospho-cAMP response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor A (VEGF-A) expression in the hippocampus. SB + ASD-1 g treatment abrogated the effects of ASD-1 g on the expression of these proteins. CONCLUSIONS: ASD-0.5 g and ASD-1 g treatments promotes neuronal survival by enhancing hippocampal neurogenesis. The effects of the ASD extract on astrocyte-associated hippocampal neurogenesis and dendritic growth are caused by the activation of p38 MAPK-mediated CREB/BDNF, GDNF, and VEGF-A signaling pathways in the hippocampus at 28 d after transient GCI.

An extractive nanoelectrospray ionization-mass spectrometry method for Chinese herbal medicine authentication.

Herein, we describe a rapid, sensitive, and nondestructive method-extractive nanoelectrospray ionization-mass spectrometry (EnESI-MS)-for traditional Chinese medicine (TCM) authentication. The mass-spectral fingerprints of volatile compounds released from various TCMs can be rapidly acquired using EnESI-MS without sample pretreatment. EnESI-MS was applied to successfully differentiate between two commonly used medicinal herbs, Schisandra chinensis and Schisandra sphenanthera, which are morphologically similar but exhibit different therapeutic effects. Specific volatile compounds of each herb in a ten-component Chinese herbal product, Jia Wei Xiao Yao San, were also identified, and the method was applied to discriminate between the commercial product and a substandard version.

Anti-Influenza Virus Activity and Chemical Components from the Parasitic Plant Cuscuta japonica Choisy on Dimocarpus longans Lour.

Dodder (Cuscuta spp.) is a parasitic weed damaging many plants and agricultural production. The native obligate parasite Cuscuta japonica Choisy (Japanese dodder) parasitizes Dimocarpus longans Lour., Ficus septica Burm. F., Ficus microcarpa L.f., Mikania micrantha H.B.K. and Melia azedarach Linn, respectively. Five Japanese dodders growing on different plants exhibit slightly different metabolites and amounts which present different pharmacological effects. Among these plants, a significant antiviral activity against influenza A virus (IAV) was found in Japanese dodder parasitizing on D. longans Lour. (CL). To further explore methanol extract components in Japanese dodder (CL), four undescribed aromatic glycosides, cuscutasides A-D (compounds 1-4) were isolated, together with twenty-six known compounds 5-30. The chemical structures of 1-4 were elucidated using a combination of spectroscopic techniques. The eighteen isolated compounds were evaluated for antiviral activity against IAV activity. Among them, 1-monopalmitin (29) displayed potent activity against influenza A virus (A/WSN/1933(H1N1)) with EC50 2.28 ± 0.04 µM and without noteworthy cytotoxicity in MDCK cells. The interrupt step of 29 on the IAV life cycle was determined. These data provide invaluable information for new applications for this otherwise harmful weed.

Cucurbitane-Type Triterpenoids from the Vines of Momordica charantia and Their Anti-inflammatory Activities.

Seven new cucurbitane-type triterpenoids, kuguaovins A-G (1-7), and five known ones were isolated from the rattans of wild Momordica charantia. Their structures were established by spectroscopic data analyses, including 1D and 2D NMR, IR, and MS techniques. The absolute configurations of the cucurbitanes were determined from NOESY data and partially by X-ray crystallographic analysis. In pharmacological studies, compounds 1-7 and 9-12 exhibited weak anti-inflammatory effects (IC50 = 15-35 µM), based on an anti-NO production assay.

A Potential Herbal Adjuvant Combined With a Peptide-Based Vaccine Acts Against HPV-Related Tumors Through Enhancing Effector and Memory T-Cell Immune Responses.

Viral infection is associated with many types of tumorigenesis, including human papillomavirus (HPV)-induced cervical cancer. The induction of a specific T-cell response against virus-infected cells is desired to develop an efficient therapeutic approach for virus-associated cancer. Chinese herbal medicine (CHM) has a long history in the treatment of cancer patients in Asian countries. Hedyotis diffusa Willd (Bai Hua She She Cao, BHSSC) is frequently used clinically and has been shown to inhibit tumor growth in vitro. However, in vivo data demonstrating the antitumor efficacy of BHSSC are still lacking. We showed that BHSSC induces murine and human antigen-presenting cell (APC) activation via the MAPK signaling pathway and enhances antigen presentation in bone marrow-derived dendritic cells (BMDCs) in vitro. Furthermore, we identified that treatment with BHSSC leads to improved specific effector and memory T-cell responses in vivo. Variant peptide-based vaccines combined with BHSSC improved antitumor activity in preventive, therapeutic, and recurrent HPV-related tumor models. Furthermore, we showed that rutin, one of the ingredients in BHSSC, induces a strong specific immune response against HPV-related tumors in vivo. In summary, we demonstrated that BHSSC extract and its active compound, rutin, can be used as adjuvants in peptide-based vaccines to increase immunogenicity and to bypass the requirement of a conditional adjuvant.

Two new diprenylated flavanones from Derris laxiflora Benth.

Phytochemical reinvestigation on the whole plants of Derris laxiflora Benth. afforded two new diprenylated flavanones, derriflavanones B and C (1-2), together with thirty-two known compounds, including sixteen flavonoids (3-18), eleven aromatic compounds (19-29), and five chlorophylls (30-34). All known compounds were first isolated from this plant. The structures of these compounds were determined by analysis of the NMR spectroscopy, mass data, IR spectra, UV spectra, optical rotation and by comparison with literature data.

A new macrocyclic diterpenoid from Anisomeles indica.

A new macrocyclic diterpenoid, 4ß,5ß-dihydroxyovatodiolide (1), together with twenty-two known compounds (2-23) were isolated from the MeOH extract of the dried aerial parts of Anisomeles indica (L.) O. Kuntze (Labiatae). The structure of 1 was established on the basis of spectral evidence. Phenylethanoids, acteoside (5) and isoacteoside (6) showed significant inhibitory to IL-2 secretion of with respect to phorbol myristate acetate and anti-CD28 monoclonal antibody co-stimulated activation of human peripheral blood T cells.

New flavonoids, emarginin A-C from Vaccinium emarginatum Hayata.

Phytochemical investigation of methanolic extract of the whole plants of Vaccinium emarginatum allowed for the characterization of one epicatechin derivative (1) that was isolated from a natural source for the first time and three new flavonoids, emarginin A (2), emarginin B (3), and emarginin C (4), together with 11 known compounds (5-15). The structures of compounds 1-4 were elucidated by combination of spectroscopic analysis (MS, IR, and NMR) and by comparison with that of literature analogues. Compounds 1-8 and 11-15 were evaluated for their preliminary in vitro anti-proliferative activity against Du145 and PC-3 prostate cancer cell lines. Among them, compound 15 exhibited most potent cytotoxicity against Du145 and PC-3 cells, with IC50 values of 8.46 and 10.98 µM, respectively. Furthermore, compounds 1-7 were assessed for their anti-inflammatory potential against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells. Compound 4 exhibited moderate anti-inflammatory activity, with an IC50 value of 27.99 µM.

Regulation effect and mechanism of Sheng-Hua-Tang on female reproductive system: From experimental transcriptomic analysis to clinical applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Sheng-Hua-Tang (SHT) is commonly used to treat female illnesses, especially postpartum conditioning. However, its effects and mechanisms on female reproductive system remain unclear. The aim of the present study was to investigate the effect of SHT on female brain-ovary-uterus axis from bench to clinic. MATERIALS AND METHODS: Mice were administrated SHT (200 mg/kg) orally for seven consecutive days. Brain, ovary, and uterus tissues were then collected for microarray analysis. A nationwide database analysis and a pilot randomized, open-label clinical trial were further applied to evaluate the clinical application and effects of SHT on postpartum women. RESULTS: Microarray analysis showed that oral administration of SHT induced a cascade reaction of gene expression, with 17, 883, and 1592 genes were significantly regulated by SHT in brain, ovary, and uterus, respectively. Population-based analysis of one million subjects in Taiwan's National Health Insurance Research Database between 1997 and 2013 showed that SHT was commonly used in menstrual disorders in female population, especially dysmenorrhea, abnormal uterine bleeding, and variation of menstrual cycle. Clinical trial on postpartum women showed that oral administration SHT for one week alleviated uterine contraction pain and breast swelling pain. Furthermore, Mmp2, Mmp3, Mmp9, Mmp11, Mmp15, Oxtr, Plrl, and Tph2 gene expression affected by SHT in mice were correlated with clinical effects of SHT in human subjects. CONCLUSION: This report provided the scientific evidences of mechanisms and clinical efficacies of SHT. Moreover, our findings might afford insights for clinical doctors in terms of SHT prescription.

New Dammarane-type Saponins from Gynostemma pentaphyllum.

Six new dammarane-type saponins, gypenosides CP1-6 (16), along with 19 known compounds 7⁻25, were isolated and characterized from the aerial parts of Gynostemma pentaphyllum. Among these compounds, eight dammarane-type saponins, 2, 5, 6, 7, 11, 12, 13, and 15, exhibited the greatest antiproliferative effects against two human tumor cell lines (A549 and HepG2).

Adjunctive Chinese herbal medicine therapy for nasopharyngeal carcinoma: Clinical evidence and experimental validation.

BACKGROUND: To investigate the benefits of adjunctive Chinese herbal medicine (CHM) for patients with nasopharyngeal carcinoma (NPC). METHODS: We included all patients diagnosed with NPC during 1997-2009 and followed until 2011 in Taiwan. We used 1:1 frequency matching by age, sex, comorbidity, conventional treatment, and index year to compare the CHM users and non-CHM users (n = 2542 each). The prescribed CHM was further investigated with regard to its cytotoxicity. RESULTS: Compared with non-CHM users, adjunctive CHM users had a lower hazard ratio of mortality risk, and a better survival probability. Gan-Lu-Yin (GLY) was the most commonly prescribed CHM, and it reduced cell viability, inhibited tumor proliferation, and induced apoptosis through the poly (ADP-ribose) polymerase and caspase-3-dependent pathway in human NPC TW01 cells. Oral administration of GLY retarded NPC-TW01 tumor growth in the xenograft nude mouse model. CONCLUSION: Real-world data and laboratory experiments implied that adjunctive CHM might be beneficial for NPC patients.

Inhibition of Amyloid Beta Aggregation and Deposition of Cistanche tubulosa Aqueous Extract.

Cistanche tubulosa aqueous extract (CTE) is already used as a botanical prescription drug for treating dementia in China. Our previous studies reported that phenylethanoid glycosides of CTE have anti-Alzheimer's disease (AD) activity by inhibiting amyloid ß peptide (Aß) aggregation and deposition. However, recent studies considered that the phenylethanoid glycosides may be metabolized by intestinal bacteria, because all analysis results showed that the bioavailability of phenylethanoid glycosides is extremely low. In this study we demonstrate how iron chelation plays a crucial role in the Aß aggregation and deposition inhibition mechanism of phenylethanoid glycosides of CTE. In addition, we further proved phenylethanoid glycosides (1⁻3) could reach brain. Active CTE component and action mechanism confirmation will be a great help for product quality control and bioavailability studies in the future. At the same time, we provide a new analysis method useful in determining phenylethanoid glycosides (1⁻3) in plants, foods, blood, and tissues for chemical fingerprint and pharmacokinetic research.

Cuscuta chinensis and C. campestris Attenuate Scopolamine-Induced Memory Deficit and Oxidative Damage in Mice.

The seeds of Cuscuta chinensis Lam. and C. campestris Yuncker have been commonly used as Chinese medical material for preventing aging. Our previous studies have found that C. chinensis and C. campestris possess anti-inflammatory activities in rodents. However, their other biological activities, such as memory-improving properties, have not yet been explored. In the present study, we examined the memory-improving effects of the extracts of C. chinensis and C. campestris on scopolamine (SCOP)-induced memory deficit and explored their underlying mechanism in mice. Both Cuscuta species improved SCOP-induced memory deficits in the passive avoidance test, elevated plus-maze, and spatial performance test of the Morris water maze in mice. In addition, compared with mice injected with SCOP, mice pretreated with both Cuscuta species stayed for a longer time on the platform for the probe test of the Morris water maze. Moreover, both Cuscuta species reduced brain acetylcholinesterase activity and malondialdehyde levels that were increased by SCOP, and the species restored the activities of antioxidant enzymes (superoxide dismutase and catalase) and the levels of glutathione that were decreased by SCOP in the brains of mice. Both Cuscuta species further decreased brain interleukin-1ß and tumor necrosis factor-α levels that were elevated by SCOP. We demonstrated that both Cuscuta species exhibited a protective activity against SCOP-induced memory deficit, cholinergic dysfunction, oxidative damage, and neuroinflammation in mice, and C. campestris has better potential than C. chinensis. In addition, we provided evidence that the seeds of C. campestris can be used as Cuscutae Semen in Traditional Chinese Medicine.

Glaulactams A-C, daphniphyllum alkaloids from Daphniphyllum glaucescens.

Glaulactams A-C (1-3), which possess a novel skeleton, as well as the known compound daphmanidin B (4), were isolated from the leaves of Daphniphyllum glaucescens and separated using ion-exchange chromatography aided by NMR fingerprinting. Their structures, including their absolute configurations, were elucidated by spectroscopic analyses and time-dependent density-functional-theory-calculated electronic circular dichroism spectra; the data were subsequently analyzed to gain insight into the respective biogenetic relationships between the isolates, which exhibited anti-H1N1 and immunosuppressive activities.

Three New Iridoid Derivatives Have Been Isolated from the Stems of Neonauclea reticulata (Havil.) Merr. with Cytotoxic Activity on Hepatocellular Carcinoma Cells.

Three new iridoids, namely neonanin A (1), neonanin B (2) and neoretinin A (3), as well as twelve known compounds, 6-hydroxy-7-methyl-1-oxo-4-carbomethoxyoctahydrocyclopenta[c]pyran (4), 4-epi-alyxialactone (5), loganetin (6), loganin (7), phenylcoumaran-α'-aldehyde (8), cleomiscosin A (9), ficusal (10), balanophonin (11), vanillic acid (12), p-coumaric acid (13), cis,trans-abscisic acid (14), and trans,trans-abscisic acid (15) were isolated from the stems of Neonauclea reticulata (Havil.) Merr. These new structures were determined by the detailed analysis of spectroscopic data and comparison with the data of known analogues. Compounds 1⁻13 were evaluated using an in-vitro MTT cytotoxic assay for hepatocellular carcinoma (HCC) cells, and the preliminary results showed that ficusal (10), balanophonin (11), and p-coumaric acid (13) exhibited moderate cytotoxic activity, with EC50 values of 85.36 ± 4.36, 92.63 ± 1.41, and 29.18 ± 3.48 µg/mL against Hep3B cells, respectively.