Enhancing oral bioavailability of andrographolide using solubilizing agents and bioenhancer: comparative pharmacokinetics of Andrographis paniculata formulations in beagle dogs.

CONTEXT: The therapeutic potential of andrographolide is hindered by its poor oral bioavailability and unpredictable pharmacokinetics, primarily due to its limited water solubility. OBJECTIVE: This work aimed to enhance the solubility and pharmacokinetics of andrographolide, a bioactive compound in Andrographis paniculata (Burm. f.) Nees (Acanthaceae), using solubilizing agents and a bioenhancer. MATERIALS AND METHODS: Four groups of beagles were compared: (1) A. paniculata powder alone (control), (2) A. paniculata powder with 50% weight/weight (w/w) ß-cyclodextrin solubilizer, (3) A. paniculata powder with 1% w/w sodium dodecyl sulfate (SDS) solubilizer, and (4) A. paniculata powder co-administered with 1% w/w SDS solubilizer and 10% piperine bioenhancer. All groups received a consistent oral dose of 3 mg/kg of andrographolide, administered both as a single dose and multiple doses over seven consecutive days. RESULTS: Thirteen chemical compounds were identified in A. paniculata powder, including 7 diterpenoids, 5 flavonoids, and 1 phenolic compound. A. paniculata co-administration with either 50% w/w ß-cyclodextrin or 1% w/w SDS, alone or in combination with 10% w/w piperine, significantly increased systemic andrographolide exposure by enhancing bioavailability (131.01% to 196.05%) following single and multiple oral co-administration. Glucuronidation is one possible biotransformation pathway for andrographolide, as evidenced by the excretion of glucuronide conjugates in urine and feces. CONCLUSION: The combination of solubilizing agents and a bioenhancer improved the oral bioavailability and pharmacokinetics of andrographolide, indicating potential implications for A. paniculata formulations and clinical therapeutic benefits. Further investigation in clinical studies is warranted.

Sub-chronic oral toxicity of a water-soluble extract of Centella asiatica (Centell-S) in Wistar rats.

BACKGROUND: Centell-S, a water-soluble extract from Centella asiatica, is predominantly composed of madecassoside and asiaticoside, exceeding 80% w/w. Pursuing its development as an herbal medicinal product, Centell-S underwent sub-chronic toxicity assessment adhering to OECD GLP 408 standards. METHODS: In a study involving 100 Wistar rats, varying doses of Centell-S (50, 200, or 800 mg/kg/day) or a vehicle control were administered orally over 90 days. To evaluate Centell-S's safety profile, assessments included clinical observations, health examinations, clinical biochemistry analyses, and detailed anatomical pathology evaluations were conducted. RESULTS: Over the 90 days of treatment, the administration of Centell-S did not lead to any fatalities in the test animals. Clinical observations did not reveal any signs indicative of toxic effects. Notably, an increase in total white blood cell and lymphocyte counts was observed in both sexes, yet these levels returned to normal following a two-week discontinuation period post-treatment. CONCLUSIONS: Under the specific conditions of the OECD GLP 408, Repeated Dose 90-day Oral Toxicity Study in Rodents, the no observed adverse effect level (NOAEL) of Centell-S was 800 mg/kg/day. These findings are promising for the continued development of Centell-S as a phytopharmaceutical for clinical applications.

Determination of Multiple Mycotoxins and Their Natural Occurrence in Edible Vegetable Oils Using Liquid Chromatography-Tandem Mass Spectrometry.

The prevalence of mycotoxins is often increased by the climatic conditions prevailing in tropical regions. Reports have revealed the contamination of mycotoxins in some types of vegetable oil. However, vegetable oil is one of the essential ingredients used in food preparation. Thus, this study determined the occurrence of multi-mycotoxins in six types of vegetable oils commercially available in Thailand to assess the consumer health risk. In total, 300 vegetable oil samples (olive oil, palm oil, soybean oil, corn oil, sunflower oil, and rice bran oil) collected from various markets in Thailand were analyzed for the presence of nine mycotoxins, namely, aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), aflatoxin G2 (AFG2), beauvericin (BEA), ochratoxin A (OTA), zearalenone (ZEA), fumonisin B1 (FB1), and fumonisin B2 (FB2) using a quick, easy, cheap, effective, rugged, and safe (QuEChERS)-based procedure and a triple quadrupole mass spectrometer equipped with an electrospray ionization source. The incidences of mycotoxin contamination varied among the different types of oil samples. AFB1, AFB2, ZEA, FB1, and FB2 were most frequently found in contaminated samples. AFB2, BEA, ZEA, FB1, and FB2 contaminated olive oil samples, whereas AFB1, AFB2, AFG2, and OTA contaminated palm oil samples. AFB1, AFB2, and ZEA were found in soybean oils, whereas ZEA, FB1, and FB2 contaminated corn oil samples. AFB1 and AFG1 contaminated sunflower oil samples, whereas AFB1, AFB2, AFG1, and OTA were detected in rice bran oil samples. However, the contamination levels of the analyzed mycotoxins were below the regulatory limits.