Biomedical subjects

K Kawabata

Publications and source records attributed to K Kawabata.

At least 55 records · Page 3Linked to original sources

PubMed2000

Elasticity mapping of living fibroblasts by AFM and immunofluorescence observation of the cytoskeleton.

Using the force mapping mode of atomic force microscopy (AFM), we measured spatial distribution of elastic moduli of living mouse fibroblasts (NIH3T3) in a physiological condition. The nuclear portion of the cellular surface is about 10 times softer than the surroundings. Stiffer fibers are confirmed in the elastic images. In order to investigate origin of the softer nuclear portion and the stiffer fibers, we fixed the identical cells imaged by the AFM, and carried out immunofluorescence observation for three types of cytoskeletal filaments--actin filaments, microtubules, and intermediate filaments, using confocal laser scanning microscopy (CLSM). A comparison between the AFM and the CLSM images revealed that the elasticity of the cells was concerned not only with the distribution of actin network, but also with intermediate filaments, whereas microtubules had no large effect on the measured elasticity.

3T3 Cells↗

PubMed2000

Comparing microscopic with macroscopic elastic properties of polymer gel

Measurements of the local elastic modulus of agar gels obtained with atomic force microscope (AFM) force mapping were compared with values obtained by the tensile creep method. The observed spatial distributions of the local elastic modulus over the gel surface in AFM elastic images clearly corresponded to the network structure of agar fibers observed both in AFM topographic and scanning electron microscope (SEM) images. Both peak and average values of distribution functions in the histograms of local elastic modulus increase monotonically with the agar concentration. Values obtained by AFM force mapping were found to be proportional to values obtained from creep experiments.

Journal Article↗

PubMed2000

Three-dimensional characterization of interior structures of exocytotic apertures of nerve cells using atomic force microscopy.

We examined the interior structure of exocytotic apertures in synaptic vesicles of neuroblastoma x glioma hybrid cells using atomic force microscopy. The atomic force microscopy detected apertures of 50-100nm in diameter at various depths within the varicosities of these cells. We were also able to image a regular radial pattern on the wall and lump-like structures at the bottom of these apertures. In contrast, scanning electron microscopy could only detect the apertures but not the fine details of their interior. The cells examined here exhibited the same electrophysiological properties and expression of synaptophysin and syntaxin 1 as presynaptic terminals, as studied by various electrophysiological and imaging techniques. Our results indicate that atomic force microscopy allows three-dimensional viewing of the fine structures located inside exocytotic apertures in nerve cells.

Calcium↗

PubMed2000

Orally active cephalosporins. Part 2: synthesis, structure-activity relationships and oral absorption of cephalosporins having a C-3 pyridyl side chain.

A series of 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamid o]cephalosporins having a pyridine ring connected through various spacer moieties at the C-3 position was designed and synthesized and evaluated for antibacterial activity and oral absorption in rats. All compounds showed potent antibacterial activity against Staphylococcus aureus, whereas antibacterial activity against gram-negative bacteria was markedly influenced by the spacer moiety between the pyridine and cephem nucleus. Oral absorption was influenced by the position of the pyridine nitrogen as well as by the spacer moiety. Among these compounds, FR86830 (14), having a 4-pyridylmethylthio moiety at the C-3 position, showed the most well balanced activity and moderate oral absorption.

Administration, Oral↗

PubMed2000

Orally active cephalosporins: synthesis, structure-activity relationships and oral absorption of 3-[(E) and (Z)-2-substituted vinyl]-cephalosporins.

A series of 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamid o]-3-[(E)- and (Z)-2-substituted vinyl]-3-cephem-4-carboxylic acids was designed and synthesized using palladium-catalyzed coupling reactions of a 3-methanesulfonyloxy-3-cephem and an E substituted vinyl stannane or Wittig reaction of a 3-triphenylphosphoniummethyl cephem and an aldehyde as a key step. These compounds were evaluated for in vitro antibacterial activity and oral absorption in rats. A number of them exhibited excellent antibacterial activity against both gram-positive and gram-negative bacteria including Haemophilus influenzae. Among them, FR86524 (2j). having a (Z)-2-(3-pyridyl)vinyl moiety at the C-3 position, had the most well balanced activity. Although FR86254 exhibited low oral absorption, the pivaloyloxymethyl ester (23) of FR86524 showed improved oral absorption.

Administration, Oral↗

PubMed2000

Effects of Fas-mediated liver cell apoptosis on diethylnitrosamine-induced hepatocarcinogenesis in mice.

The present study was designed to investigate the effect of Fas-mediated liver cell apoptosis, induced by a hamster monoclonal antibody against mouse Fas antigen, on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. DEN (10 microg g(-1), intraperitoneally (i.p.)) was given to 15-day-old male C3H/HeJ mice. Three weeks after DEN treatment, Fas-mediated liver cell apoptosis induced by anti-Fas antibody resulted in a biphasic effect on induction of liver cell tumours, depending on dosage and time of antibody administration. Single or multiple treatment with high dose anti-Fas antibody (5 microg animal(-1)), induced gross liver cell damage and decreased the incidence of liver cell tumours in DEN-treated mice. In contrast, five treatments with low dose anti-Fas antibody (2 microg animal(-1)), induced dispersed localized liver cell damage and promoted the number of large-sized liver cell adenomas and hepatocellular carcinomas. These findings suggest that high dose anti-Fas antibody has a marked effect on the clearance of DEN-initiated liver cells, whereas repeated administration of low dose anti-Fas antibody promotes hepatocarcinogenesis. It is concluded that Fas-mediated liver cell apoptosis has a biphasic effect on hepatocarcinogenesis.

Adenoma↗

PubMed2000

Suppression by citrus auraptene of phorbol ester-and endotoxin-induced inflammatory responses: role of attenuation of leukocyte activation.

Auraptene (AUR), a citrus coumarin derivative, is one of the promising chemopreventive agents against skin, tongue, esophagus and colon carcinogenesis in rodents. We reported previously that AUR suppresses superoxide anion (O(2)(-)) generation from inflammatory leukocytes in in vitro experiments. In the present study, we investigated the anti-inflammatory activities of AUR using a 12-O:-tetradecanoylphorbol-13-acetate-treated mouse skin model, and compared them with those of umbelliferone (UMB), a structural analog of AUR that is virtually inactive toward O(2-) generation inhibition. Double pre-treatments of mouse skin with AUR, but not UMB, markedly suppressed edema formation, hydrogen peroxide production, leukocyte infiltration, and the rate of proliferating cell nuclear antigen-stained cells. These inhibitory effects by AUR are attributable to its selective blockade of the activation stage, as revealed by single pre-treatment experiments. In a murine macrophage line, RAW 264.7, AUR significantly attenuated the lipopolysaccharide-induced protein expression of inducible isoforms of both nitric oxide synthase and cyclooxygenase, with decreased production of nitrite anion and prostaglandin E(2), and yet suppressed the release of tumor necrosis factor-alpha. Conversely, UMB did not show any inhibitory effect. This contrasting activity profile between AUR and UMB was rationalized to be a result of their distinct differences in cellular uptake efficiencies, i.e. the geranyloxyl group in AUR was found to play an essential role in incorporation. Thus, our findings indicate that AUR is an effective agent to attenuate the biochemical responsiveness of inflammatory leukocytes, which may be essential for a greater understanding of the action mechanism that underlies its inhibition of inflammation-associated carcinogenesis.

Animals↗

PubMed2000

Quantitative analyses of topography and elasticity of living and fixed astrocytes.

The topography and elasticity of living and fixed astrocytes cultured from the rat cerebra were studied quantitatively by atomic force microscopy (AFM). Ridge-like structures reflecting F-actin beneath the cell membrane were prominent in the contact-mode images of living astrocytes. Many of these ridges became unclear after fixation (2% glutaraldehyde). In addition, the ridge-like structures were invisible in the topography of living cells observed at zero-loading force in the force mapping mode, which is considered to show the real cell surface not pressed down by an AFM tip. The topography of fixed cells observed both in the contact mode and at zero-loading force in the force mapping mode was similar to that of living cells observed at zero-loading force in the force mapping mode, although some deformed areas were detected in the fixed cells. The elasticity map images of living astrocytes showed that the cell membrane above the nucleus was softer (2-3 kPa) than the surroundings, and that the cell membrane above F-actin was stiffer (10-20 kPa) than the surroundings. In the elasticity map images of fixed astrocytes, on the other hand, the elasticity of the cells was found to be relatively uniform (200-700 kPa) irrespective of the inner structures of cells. These results show that images observed by AFM should be carefully examined in consideration of the force introduced to specimens and the elasticity of specimens to find out the real surface topography.

Actins↗

PubMed2000

Time-lapse viscoelastic imaging of living fibroblasts using force modulation mode in AFM.

Using the force modulation mode in atomic force microscopy, we have succeeded in capturing time-lapse viscoelastic images of living mouse fibroblasts (NIH3T3) for several hours in a physiological condition without damaging the fibroblasts. Elongation of the lamellipodia and swelling of blebs were observed in time-lapse topographic images, which were taken every 10 min. The corresponding viscoelastic responses at a frequency of 600 Hz were visualized as consecutive images. The stiffer part of the cell body was fairly stable and did not show morphological changes for over 1 h. This is probably due to excess condensation of the actin network, hardening the cell cortex, and lowering the cytoskeletal activity. The nuclear portion of the cell body seems to be slightly less viscous than the peripheral region.

3T3 Cells↗

PubMed2000

Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10.

To clarify the neuroendocrine differentiation and CD10 expression in solid-pseudopapillary tumors (SPTs) of the pancreas, we performed immunohistochemical analysis in 19 such tumors, including one solid-pseudopapillary carcinoma (SPC), along with 20 pancreatic neuroendocrine tumors (PNTs), six acinar cell carcinomas (ACCs), and one pancreatoblastoma (PB). We used antisera directed against CD56, synaptophysin, protein gene product 9.5, the alpha-subunit of Go protein, chromogranin A, CD10, trypsin, chymotrypsin, various cytokeratins (CKs), CA19-9, vimentin, and alpha-1-antitrypsin (AAT). All SPTs exhibited immunoreactivity for CD56 and CD10, and 15 expressed other neuroendocrine markers focally with the exception of chromogranin A. Frequent clustering of synaptophysin-positive cells was noted. Two cases contained a peculiar nodule that cytomorphologically and immunohistochemically resembled PNT. CD10-positive cells were scarce in one SPC. PNTs were CD56-positive, but often with faint intensity, and staining for other neuroendocrine markers, including chromogranin A, was diffusely positive. CD10 was detected, mostly in a focal pattern, in five PNTs. Pan-CK, CK8, CK18, and CK19 were more frequently demonstrated in PNT than SPT. Vimentin and AAT were often identified in PNT as well and were not specific for SPT. ACCs were CD56-negative, with the exception of one case designated as a mixed acinar-endocrine carcinoma. PB was focally positive for CD56 at the periphery of the tumor nests. Four ACCs and one PB exhibited focal CD10 reactivity. This study demonstrated the unique immunohistochemical features of SPT. Our results also suggest that SPT exhibits, at least focally, neuroendocrine differentiation, and that these neuroendocrine markers and CD10 are diagnostically useful.

Adolescent↗

PubMed2000

Combination effect of photodynamic and sonodynamic therapy on experimental skin squamous cell carcinoma in C3H/HeN mice.

We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide-a derivative PH-1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX-70, a commonly used sonosensitizer. Mice were injected with either PH-1126 or ATX-70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX-70) or 36 hr (PH-1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX-70; 44J/cm2 of 650 nm for PH-1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH-1126 or ATX-70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92-98%) (additive effect) as compared to either single treatment (27-77%). The combination using PH-1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT-treated mice (> 120 days) was significantly greater than that in single treatment groups (77-95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2-3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non-superficial or nodular tumors.

Animals↗

PubMed2000

Chemopreventive effect of bovine lactoferrin on 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats.

The modifying effects of dietary feeding of bovine lactoferrin (bLF) on tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. The activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and quinone reductase (QR), polyamine content and ornithine decarboxylase (ODC) activity in the tongue were also examined for mechanistic analysis of possible modifying effects of bLF on carcinogenesis. At 7 weeks of age, all animals except those treated with bLF alone and untreated rats were given 20 ppm 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 7 days before 4-NQO exposure, experimental groups were fed experimental diets containing bLF (0.2% and 2%) for 10 weeks ("initiation feeding"). Starting 1 week after the cessation of exposure to 4-NQO, the other experimental groups given 4-NQO and a basal diet were fed the experimental diets for 22 weeks ("postinitiation feeding"). At week 32, the incidence and multiplicity of tongue neoplasms in the "initiation feeding" groups of 0.2% and 2% bLF and the "post-initiation feeding" group of 0.2% bLF were lower than those of the 4-NQO alone group, but without statistical significance. However, "post-initiation feeding" of 2% bLF caused a significant reduction in the incidence (20% vs. 55%, P=0.02418) and multiplicity (0.25+/-0.54 vs. 0.70+/-0.71, P<0.05) of tongue squamous cell carcinoma (by 64%, P=0.02418). bLF treatment elevated liver and tongue GST activities and liver QR activity. The "post-initiation feeding" with 2% bLF significantly decreased QR activity, proliferating cell nulcear antigen-positive index and ODC activity in the tongue. In addition, feeding with bLF decreased tongue polyamine content. These results suggest that bLF, when given at the 2% dose level during the post-initiation phase, exerts chemopreventive action against tongue tumorigenesis through modification of cell proliferation activity and/or the activities of detoxifying enzymes.

4-Nitroquinoline-1-oxide↗

PubMed2000

Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1'-acetoxychavicol acetate.

The modifying effects of 1'-acetoxychavicol acetate (ACA) on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis were investigated in male F344 rats. At 5 weeks of age, all test animals, except those given the test chemical alone, and the control rats received s.c. injections of NMBA (0.5 mg/kg body weight/injection, three times per week) for 5 weeks. At the termination of the study (20 weeks), 75% of rats treated with NMBA alone had esophageal neoplasms (papillomas). However, the groups given a dose of 500 ppm ACA during the initiation phase developed a significantly reduced incidence of tumors (29%; P<0.01). Exposure to ACA (500 ppm) during the post-initiation phase also decreased the frequency of the tumors (38%; P<0.05). A reduction of the incidence of preneoplastic lesions (hyperplasia or dysplasia) was obtained when ACA was administered in the initiation phase (P<0.01). Cell proliferation in the esophageal epithelium, determined by assay of proliferating cell nuclear antigen (PCNA), was lowered by ACA (P<0.05). Blood polyamine contents in rats given NMBA and the test compound were also smaller than those of rats given the carcinogen (P<0.05). These findings suggest that dietary ACA is effective in inhibiting the development of esophageal tumors by NMBA when given during the initiation or post-initiation phase, and such inhibition is related to suppression of cell proliferation in the esophageal epithelium.

Animals↗

PubMed2000

Chemopreventive effect of curcumin on N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats.

Modifying effects of curcumin (derived from the rhizome of Curcuma longa L.) during the initiation or post-initiation phase of N-nitrosomethylbenzylamine (NMBA)-induced esophageal carcinogenesis were investigated in male F344 rats. Five-week-old rats were divided into 5 groups, and groups 1, 2 and 3 were given intraperitoneal injections of NMBA (0.5 mg / kg body weight / injection 15 times) for 5 weeks from 7 weeks old to induce esophageal neoplasms. Groups 2 and 3 were fed the diet containing 500 ppm curcumin during the initiation and post-initiation phases, respectively. Group 4 was given the diet containing curcumin throughout the experiment, and group 5 was kept on the basal diet alone and served as an untreated control. Incidence and multiplicity of esophageal neoplasms of group 1 (NMBA alone) were 66.7% and 0.83 +/- 0.70, respectively. Those of groups 2 and 3 were significantly less than those of group 1 (39.3%, 0.46 +/- 0.64, P < 0.05; 33.3%, 0.36 +/- 0.56, P < 0.05, respectively). Furthermore, the incidence and multiplicity of esophageal preneoplastic lesions (moderate or severe epithelial dysplasia) of group 2 (57.1%, 0.61 +/- 0.57; 40%, 0.29 +/- 0.46) or 3 (56.7%, 0.67 +/- 0.66; 23.3%, 0.23 +/- 0.43) were less than those of group 1 (100%, 1.67 +/- 0.70; 70.8%, 0.92 +/- 0.72) (P < 0.05). In this experiment, feeding of curcumin significantly decreased the expression of cell proliferation biomarkers (5-bromo-2'-deoxyuridine labeling index) in the non-lesional esophageal epithelium (P < 0.01). These findings indicate that curcumin inhibits NMBA-induced esophageal carcinogenesis when given during the post initiation as well as initiation phase. This inhibition may be related to suppression of the increased cell proliferation induced by NMBA in the esophageal epithelium.

Animals↗

PubMed2000

In vitro activities of a new lipopeptide antifungal agent, FK463, against a variety of clinically important fungi.

The in vitro antifungal activity and spectrum of FK463 were compared with those of amphotericin B, fluconazole, and itraconazole by using a broth microdilution method specified by National Committee for Clinical Laboratory Standards document M27-A (National Committee for Clinical Laboratory Standards, Wayne, Pa., 1997). FK463 exhibited broad-spectrum activity against clinically important pathogens including Candida species (MIC range, <==0.0039 to 2 microg/ml) and Aspergillus species (MIC range, <==0.0039 to 0.0313 microg/ml), and its MICs for such fungi were lower than those of the other antifungal agents tested. FK463 was also potently active against azole-resistant Candida albicans as well as azole-susceptible strains, and there was no cross-resistance with azoles. FK463 showed fungicidal activity against C. albicans, i.e., a 99% reduction in viability after a 24-h exposure at concentrations above 0.0156 microg/ml. The minimum fungicidal concentration (MFC) assays indicated that FK463 was fungicidal against most isolates of Candida species. In contrast, the MFCs of FK463 for A. fumigatus isolates were much higher than the MICs, indicating that its action is fungistatic against this species. FK463 had no activity against Cryptococcus neoformans, Trichosporon species, or Fusarium solani. Neither the test medium (kind and pH) nor the inoculum size greatly affected the MICs of FK463, while the addition of 4% human serum albumin increased the MICs for Candida species and A. fumigatus more than 32 times. Results from preclinical in vitro evaluations performed thus far indicate that FK463 should be a potent parenteral antifungal agent.

Antifungal Agents↗

PubMed2000

Ischemic preconditioning prevents I/R-induced alterations in SR calcium-calmodulin protein kinase II.

Although Ca(2+)/calmodulin-dependent protein kinase II (CaMK II) is known to modulate the function of cardiac sarcoplasmic reticulum (SR) under physiological conditions, the status of SR CaMK II in ischemic preconditioning (IP) of the heart is not known. IP was induced by subjecting the isolated perfused rat hearts to three cycles of brief ischemia-reperfusion (I/R; 5 min ischemia and 5 min reperfusion), whereas the control hearts were perfused for 30 min with oxygenated medium. Sustained I/R in control and IP groups was induced by 30 min of global ischemia followed by 30 min of reperfusion. The left ventricular developed pressure, rate of the left ventricular pressure, as well as SR Ca(2+)-uptake activity and SR Ca(2+)-pump ATPase activity were depressed in the control I/R hearts; these changes were prevented upon subjecting the hearts to IP. The beneficial effects of IP on the I/R-induced changes in contractile activity and SR Ca(2+) pump were lost upon treating the hearts with KN-93, a specific CaMK II inhibitor. IP also prevented the I/R-induced depression in Ca(2+)/calmodulin-dependent SR Ca(2+)-uptake activity and the I/R-induced decrease in the SR CaMK II activity; these effects of IP were blocked by KN-93. The results indicate that IP may prevent the I/R-induced alterations in SR Ca(2+) handling abilities by preserving the SR CaMK II activity, and it is suggested that CaMK II may play a role in mediating the beneficial effects of IP on heart function.

Animals↗

PubMed2000

Delayed neutrophil elastase inhibition prevents subsequent progression of acute lung injury induced by endotoxin inhalation in hamsters.

To define the role of neutrophil elastase (NE) in the progression of acute lung injury (ALI), we examined the effects of post-treatment with a specific NE inhibitor, sivelestat sodium hydrate (sivelestat), on ALI induced by endotoxin (ET) inhalation in hamsters. Inhalation of ET (300 microg/ml, 30 min) in conscious hamsters increased inflammatory cell count, protein concentration, and hemorrhage in bronchoalveolar lavage fluid (BALF) that peaked 24 h after ET inhalation. These changes were significant 2 h after ET inhalation and paralleled the increase in NE activity in BALF. When intravenously infused from 2 to 24 h post-ET inhalation, sivelestat (0.03 to 3 mg/kg/h) dose-dependently attenuated changes in these BALF parameters at 24 h post-ET inhalation in a manner dependent on the inhibition of NE activity in BALF. Histopathological analysis also indicated that sivelestat prevented the progression of lung inflammation such as alveolar neutrophil infiltration and hemorrhage. In contrast, dexamethasone (3 mg/kg, intravenously) was not effective in this model when administered 2 h after ET inhalation, although it was highly effective when applied before ET. We conclude that delayed inhibition of NE activity with sivelestat prevents subsequent progression of ALI in hamsters after ET inhalation. Thus NE may play an important role in the progression of ALI.

Animals↗

PubMed2000

Baicalin, the predominant flavone glucuronide of scutellariae radix, is absorbed from the rat gastrointestinal tract as the aglycone and restored to its original form.

When baicalin was orally administered to conventional rats, it was detected in their plasma for 24 h after administration, but baicalein, the aglycone of baicalin, was not detected. However, when baicalin was given to germ-free rats, only a small amount of baicalin was detected in their plasma within 2 h after the administration, its AUC0-lim (the area under the concentration-time curve from 0 to last determination time) being 12.0% of that in conventional rats. Subsequently, a considerable amount (55.1 +/- 6.2%) of baicalin was recovered from the gastrointestinal tract even 4 h after administration. When baicalein was orally administered to conventional rats, however, baicalin appeared rapidly in their plasma at an AUC0-lim value similar to that obtained after oral administration of baicalin, despite the absence of baicalein in plasma. When intestinal absorption was evaluated by the rat jejunal loop method, baicalein was absorbed readily, but only traces of baicalin were absorbed. Moreover, in conventional rats a small amount (13.4 +/- 3.1%) of baicalin and an appreciable amount (21.9 +/- 3.4%) of baicalein were recovered from the gastrointestinal tract even 4 h after oral administration of baicalin, but only a small amount (3.93 +/- 1.43%) of baicalein was detected in the intestinal tract 1 h after administration of baicalein. Baicalin was transformed to baicalein readily by the rat gastric and caecal contents. When baicalin was administered orally to conventional rats, an appreciable amount of baicalein was recovered in their gastrointestinal tracts. Moreover, baicalein was efficiently conjugated to baicalin in rat intestinal and hepatic microsomes. These results indicate that baicalin itself is poorly absorbed from the rat gut, but is hydrolysed to baicalein by intestinal bacteria and then restored to its original form from the absorbed baicalein in the body.

Administration, Oral↗