Baihuasheshecao(Hedyotis diffusa) is a commonly used traditional Chinese medicine derived from the whole herb of H. diffusa and has been widely utilized in folk medicine. It possesses anti-tumor, antibacterial, and anti-inflammatory properties, making it one of the frequently used herbs in TCM clinical practice. However, Shuixiancao(H. corymbosa) and Xianhuaercao(H. tenelliflora), species of the same genus, are often used as substitutes for Baihuasheshecao. To substantiate the medicinal basis of Baihuasheshecao, this study systematically reviewed classical herbal texts and modern literature, examining its nomenclature, botanical origin, harvesting, processing, properties, meridian tropism, pharmacological effects, and clinical applications. The results indicate that Baihuasheshecao was initially recorded as "Shuixiancao" in Preface to the Indexes to the Great Chinese Botany(Zhi Wu Ming Shi Tu Kao). Based on its morphological characteristics and habitat description, it was identified as H. diffusa in the Rubiaceae family. Subsequent records predominantly refer to it as Baihuasheshecao as its official name. In most regions, Baihuasheshecao is recognized as the authentic medicinal material, distinct from Shuixiancao and Xianhuaercao. Baihuasheshecao is harvested in late summer and early autumn, and the dried whole plant, including its roots, is used medicinally. The standard processing method involves cutting. It is known for its effects in clearing heat, removing toxins, reducing swelling and pain, and promoting diuresis to resolve abscesses. Initially, it was mainly used for treating appendicitis, intestinal abscesses, and venomous snake bites, and later, it became a treatment for cancer. The excavation of its clinical value followed a process in which overseas Chinese introduced the herb from Chinese folk medicine to other countries. After its unique anti-cancer effects were recognized abroad, it was reintroduced to China and gradually became a crucial TCM for cancer treatment. The findings of this study help clarify the historical and contemporary uses of Baihuasheshecao, providing literature support and a scientific basis for its rational development and precise clinical application.
Humans ; China ; Drugs, Chinese Herbal/chemistry* ; Hedyotis/classification* ; Medicine, Chinese Traditional/history*

OBJECTIVES: To investigate the active ingredients in Hedyotis diffusa-Scutellaria barbata D. Don and the main biological processes and signaling pathways mediating their inhibitory effect on primary hepatocellular carcinoma (HCC). METHODS: The core intersecting genes of HCC and the two drugs were screened from TCMSP, Uniport, Genecards, and String databases using Cytoscape software, and GO and KEGG enrichment analyses of the intersecting genes were conducted. Molecular docking between the active ingredients of the drugs and the core genes was carried out using Pubcham, RCSB and Autoduckto to identify the active ingredients with the highest binding energy, whose inhibitory effect on HepG2 cells was verifies using CCK-8 assay, flow cytometry and Western blotting. RESULTS: TP53 and ESR1 were identified as the core genes of HCC and the two drugs. GO and KEGG analyses showed that the two genes were mainly involved in regulation of apoptotic signaling pathway, cell population proliferation, methane raft, and protein kinase activity, and participated in the signaling pathways of apoptosis, proteoglycans in cancer, PI3K Akt signaling pathway, and hepatitis B. Molecular docking studies showed that the active ingredients of the drugs could be docked with TP53 and ESR1 genes under natural conditions, and ursolic acid had the highest binding energy to ESR1 (-4.98 kcal/mol). The results of CCK-8 assay, flow cytometry and Western blotting all demonstrated significant inhibitory effect of ursolic acid on HepG2 cells. CONCLUSIONS The inhibitory effect of Hedyotis diffusa-scutellariae barbatae on HCC is mediated by multiple active ingredients in the two drugs.
Humans ; Molecular Docking Simulation ; Liver Neoplasms/drug therapy* ; Hep G2 Cells ; Network Pharmacology ; Carcinoma, Hepatocellular/drug therapy* ; Hedyotis/chemistry* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Tumor Suppressor Protein p53/metabolism* ; Apoptosis/drug effects* ; Estrogen Receptor alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology*

This study aimed to investigate the chemical constituents in the water extract of the whole herb of Hedyotis scandens by silica gel, ODS, and MCI column chromatographies together with preparative high-performance liquid chromatography(HPLC). The structures of isolated constituents were identified by NMR, HR-ESI-MS, etc. Thirteen compounds were isolated and identified as methyl 4-benzoyloxy-3-methoxybenzeneacetate(1), 4-benzoyloxy-3-methoxybenzeneacetic acid(2), 3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(3), salicylic acid(4), 3-hydroxy-4-methoxypyridine(5), syringic acid(6), hydroxycinnamic acid(7),(R)-6-methyl-4,6-bis(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde(8), 1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(9), 1H-indole-3-carboxaldehyde(10), isoscopoletin(11), syringaresinol(12), and pinoresinol(13). Among them, compounds 1 and 2 were new phenolic acid compounds, compounds 3-5, 8-11, and 13 were isolated from this genus for the first time, and compounds 6, 7, and 12 were obtained from H. scandens for the first time. The activity test showed that compounds 1 and 10 had a certain inhibitory effect on Mycobacterium smegmatis, with MIC_(50) values of 58.5 and 33.3 μg·mL~(-1), respectively.
Hedyotis/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Magnetic Resonance Spectroscopy ; Salicylic Acid

Hedyotis hedyotidea has been traditionally used for the treatment of arthritis, cold, cough, gastro-enteritis, headstroke, etc. But few studies have screened the active compounds from extracts of H. hedyotidea. In this study, the structure of the chemical constituents from stems of H. hedyotidea were determined and the immunosuppressive activity of the compounds was evaluated. The compounds were separated and purified with silica gel, gel column chromatographies and preparative HPLC, and their structures were identified by spectral methods such as MS and NMR. Eleven compounds were obtained and identified as(6S,9S) -vomifoliol (1), betulonic acid (2), betulinic acid (3), betulin(4), 3-epi-betulinic acid (5), ursolic acid (6), β-sitosterol (7), stigmast-4-en-3-one (8), 7β-hydroxysitosterol (9), (3β,7β) -7-methoxystigmast-5-en-3-ol (10) and morindacin (11). This is the first report of compounds 1, 2, 4, 8, 9, 10 and 11 from H. hedyotidea. Compounds 1, 2 and 8-11 were firstly isolated from the genus Hedyotis, and compounds 9 and 10 were isolated from the family Rubiaceae for the first time. The immunosuppressive activity of these compounds was tested using the lymphocyte transsormationtest. Compounds 4, 6 and 9 showed significant immunosuppressive activity.
Animals ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Hedyotis ; chemistry ; Immunosuppressive Agents ; chemistry ; isolation & purification ; pharmacology ; Lymphocytes ; drug effects ; immunology ; Male ; Mass Spectrometry ; Mice ; Mice, Inbred C57BL ; Molecular Structure ; Plant Stems ; chemistry

OBJECTIVE: To explore the proliferation inhibition and apoptosis of polysaccharides extracts from polysaccharides extracts from Hedyotic diffusa (PEHD) on Human Nasopharyngeal Carcinoma (NPC)cell line CNE2 cells in vitro. METHOD: CNE2 cells treated with various concentrations of PEHD were detected by MTT assay at 24 h, 48 h, and 72 h. The apoptotic cells were analyzed by flow cytometry with Annexin V/PI staining. The expression levels of Bax, Bcl-2 and caspase-3 protein were examined by Western blotting method. RESULT: The growth of CNE2 cells were suppressed after treatment with PEHD (P < 0.05), MTT assay showed that the highest cell inhibition rate reached to 76.5%, the inhibition in the doses from 2 to 6 mg/ml showed dose-and-time-dependent. The percent of apoptosis in 4 and 6 mg/ml PEHD treatment groups for 48 h were 31.32%, 46.28%, respectively, and significantly higher than that in control groups, 4.86% (P < 0.01). After the cells being treated with PEHD for 48 h, the expression of Bax and caspase-3 protein increased, and the expression of Bcl-2 protein decreased gradually. CONCLUSION PEHD could inhibited the growth of CNE2 cells and was dose-and-time-dependent, the mechanism may involve induction of cell apoptosis, which was associated with the activation of Bax and caspase-3 protein and the down-regulation of Bcl-2 protein expression.
Apoptosis ; Carcinoma ; Caspase 3 ; metabolism ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Down-Regulation ; Hedyotis ; chemistry ; Humans ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; pathology ; Plant Extracts ; pharmacology ; Polysaccharides ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo explore the proliferation inhibition and apoptosis effects of polysaccharides extracts from Hedyotis diffusa (PEHD) on multiple myeloma (MM) cell line RPMI 8226 cells in vitro, so as to provide experimental theory for the clinical application in the treatment of MM.

METHODSMTT assay was used to examine the effects of PEHD on cell growth. The apoptotic cells were analyzed by flow cytometry with AnnexinⅤ/PI staining. Hoechst staining was used to observe the morphological changes of RPMI 8226 cell apoptosis. The expression levels of caspase-3,-8,-9, PARP, nucleoprotein NF-κB protein and other channel protein were assayed by Western blotting method.

RESULTSThe growth of RPMI 8226 cells were suppressed after treatment with PEHD, the highest inhibition rate reached to 92.3%, the results in the doses from 1 to 4 mg/ml showed a dose-and-time-dependent manner. The proportion of apoptotic cells in 1, 2 and 3 mg/ml PEHD treatment groups for 24 h were 22.52%, 62.31% and 69.94%, respectively, and significantly higher than that of control 8.93%. After treated with PEHD, apoptotic body appeared in RPMI 8226 cells nucleus and the number of apoptotic body increased in a dose-dependent manner. With the increasing of PEHD concentration, the expression of caspase-8,-9,-3 and PARP protein increased. The expression of Mcl-1, Bcl-xl, Bid and Bim protein decreased gradually, but the expression of Bax, Bak and Bad protein increased, and the expression of p-AKT protein (60 kDa) and NF-κB obviously decreased.

CONCLUSIONPEHD could inhibited the growth of RPMI 8226 cells and displayed a dose-and-time-dependent manner, its mechanism may involve cell apoptosis induction, which was associated with the activation of caspase-8, caspase-9, and caspase-3 protein and the down-regulation of p-AKT and NF-κB protein expression.

Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Hedyotis ; chemistry ; Humans ; Multiple Myeloma ; metabolism ; pathology ; NF-kappa B ; metabolism ; Polysaccharides ; pharmacology ; Proto-Oncogene Proteins c-akt ; metabolism

OBJECTIVETo analyze p-coumaril acid, trans-6-O-p-coumaroyl scandoside methyl ester and its metabolites in rat plasma after intragastric administration of exocarpium Diffusa effective extracts.

METHODRat blood samples were collected 1.0 h after oral administration of 0.4 g x kg(-1) exocarpium Diffusa effective extracts, and then were analyzed by using HPLC-Q-TOF-MS.

RESULTIn rat plasma, only one metabolite was detected. The structure was identified by reference substance to be p-coumaril acid.

CONCLUSIONThe methyl glucoside metabolite in rat from the main component parts of trans-6-O-p-coumaroyl scandoside methyl ester droppings of vines in Diffusa effective extracts is p-coumaril acid. This experiment provides a theortical basis for studying chemical compositions and pharmacodynamic action of Diffusa.

Animals ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; metabolism ; Hedyotis ; chemistry ; Male ; Mass Spectrometry ; methods ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effects of three Chinese herbal antidotes, i.e. Herba Artemisiae annuae (A), Herba Hedyotis diffusae (H) and Rhizoma Cimicifugae (C), all were ingredients of Jiedu Quyu Ziyin Recipe, for adjusting the regulated on activation normal T cell expressed and secreated (RANTES), gene expression in serum and renal tissue of MRL/lpr mice.

METHODSFifty-four MRL/lpr mice were randomized into 9 groups, with 6 in each, and intragastrically infused with A, H, C, A+H, H+C, A+C, A+H+C (all in dosage-form of decoction), prednisone suspension and physiological saline, respectively for 12 weeks. RANTES expression in serum and renal tissue of animals were detected with ELISA and RT-PCR at the end of the study.

RESULTSLevels of RANTES expression was significantly reduced in the prednisone treated group after treatment. Excepting no significant change being observed in the groups treated with A and C, the changes in the other groups were all milder than those in the group treated with A+H+C.

CONCLUSIONChinese herbal antidotes A, H and C in combination can significantly inhibit the RANTES expression in serum and renal tissue of MRL/lpr mice.

Animals ; Artemisia annua ; chemistry ; Chemokine CCL5 ; blood ; metabolism ; Cimicifuga ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hedyotis ; chemistry ; Kidney ; metabolism ; Mice ; Mice, Inbred MRL lpr ; T-Lymphocytes ; immunology ; metabolism

OBJECTIVETo investigate the chemical constituents from Hedyotis diffusa.

METHODThe compounds were isolated and purified by various chromatographic techniques and identified by their physicochemical properties and spectral data.

RESULTEight compounds had been reported in last paper, and this time eight more compounds were isolated and identified as 6-hydroxystigmasta-4,22-dien-3-one (1), 3-hydroxystigmasta-4,22-dien-7-one (2), 2-hydroxy-3-methylanthraquinone (3), 2,6-dihydroxy-3-methyl-4-methoxyanthraquinone (4), iso-scutellarein (5), isoetin (6), aesculetin (7), gypsogenic acid (8).

CONCLUSIONCompounds 1-3, 5-8 were obtained from the genus Hedyotis for the first time.

Hedyotis ; chemistry ; Organic Chemicals ; analysis ; isolation & purification

OBJECTIVETo develop an HPLC method for determination of scandoside methyl ester in Hedyotis chrysotricha.

METHODThe determination was carried out on an HC-C18 column elnted with acetonitrile-water (7:93) as mobile phase, and the detection wavelength was set at 238 nm.

RESULTThere is a good linearity in the range 22.08-552 mg L(-1) of scandoside methyl ester and the average recovery is 97.7% (n = 6), RSD 0.72%.

CONCLUSIONThis method is convenient, quick, and is applicable to the quality control of H. chrysotricha.

Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Esters ; analysis ; Hedyotis ; chemistry