Oral sub-chronic toxicity of fingerroot (Boesenbergia rotunda) rhizome extract formulation in Wistar rats.

Background: Boesenbergia rotunda (fingerroot) rhizome extract contains two major bioactive components, panduratin A and pinostrobin. In our previous study, we found the anti-inflammatory effects of the fingerroot extract against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in golden Syrian hamsters. In the present study, we evaluated the sub-chronic toxicity of a fingerroot extract formulation over 90 consecutive days of oral administration. Methods: We enhanced the water solubility of a fingerroot extract by formulating it with cyclodextrin, containing panduratin A (29% w/w) and pinostrobin (32% w/w). This formulation was administered to male and female Wistar rats at doses of 25, 50, or 100 mg/kg/day for a duration of 90 days. Additionally, two recovery groups, comprising a control group and a high-dose group, were designated for a 14-day observation period to assess the persistence and reversibility of potential adverse effects. Throughout the experiment, we performed clinical and health observations, followed by hematological testing, clinical biochemistry analysis, necropsy examination, and histopathological evaluation at the end of the experiment. Results: The administration of the fingerroot extract formulation at doses of 25, 50, or 100 mg/kg/day did not result in mortality or clinical signs of toxicity. No clinically significant findings were associated with the oral administration of the fingerroot extract formulation. Conclusion: The fingerroot extract formulation showed no serious adverse effects at doses up to 100 mg/kg/day in Wistar rats under the experimental condition. Consequently, the No Observed Adverse Effect Level (NOAEL) was considered to be 100 mg/kg/day. This finding contributes significance for future developments involving fingerroot extract in herbal medicinal products targeting chronic inflammation.

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.

Absolute oral bioavailability and possible metabolic pathway of panduratin A from Boesenbergia rotunda extract in beagle dogs.

CONTEXT: Attempts are ongoing to develop medications to fight against the COVID-19 pandemic. Our previous study revealed the in vitro anti-SARS-CoV-2 activity of fingerroot [Boesenbergia rotunda (L.) Mansf. (Zingiberaceae)] and its phytochemical, panduratin A. OBJECTIVE: To investigate the pharmacokinetic profiles of panduratin A as a pure compound and in a fingerroot extract formulation in beagle dogs. MATERIALS AND METHODS: A total of 12 healthy dogs were randomly divided into three groups, a single dose of 1 mg/kg panduratin A by intravenous and multiple doses of 5 and 10 mg/kg panduratin A fingerroot extract formulation by oral administration for seven consecutive days. The plasma concentration of panduratin A was determined by LCMS. RESULTS: The peak concentrations of a single dose of 5 and 10 mg/kg panduratin A fingerroot extract formulation were 12,416 ± 2,326 and 26,319 ± 8,221 µg/L, respectively. Increasing the oral dose of fingerroot extract formulation, equivalent to panduratin A 5-10 mg/kg, showed dose proportionality, with an approximately 2-fold increase in Cmax and AUC. The absolute oral bioavailability of panduratin A in the fingerroot extract formulation was approximately 7-9%. The majority of panduratin A was biotransformed into several products via oxidation and glucuronidation, and predominantly excreted via the faecal route. CONCLUSION: The oral formulation of fingerroot extract was safe in beagle dogs, and increasing dose showed dose proportionality in terms of the systemic exposure of panduratin A. This information will support the phytopharmaceutical product development of fingerroot extract against the COVID-19 pandemic.