Acute and Subacute Toxicity Assessment of Andrographolide-2-hydroxypropyl-β-cyclodextrin Complex via Oral and Inhalation Route of Administration in Sprague-Dawley Rats

Singh, Shashi Chandrama; Choudhary, Muskan; Mourya, Atul; Khatri, Dharmendra Kumar; Singh, Pankaj Kumar; Madan, Jitender; Singh, Harshpal

doi:10.1155/2022/6224107

Cited by 9 publications

(6 citation statements)

References 35 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The delivery of Dyngo4a and mβCD via nasal spray directly introduces the drugs to the desired target (respiratory system) in contrast to drugs that are injected or ingested. Given the ability of mβCD to solubilize various drugs, it is currently widely used as a vehicle for enhancing drug delivery via nebulization ( Evrard et al, 2004 ; Chandrama Singh et al, 2022 ). Nebulization with Dyngo4a and mβCD could also be used in conjunction with other therapies, such as antisense oligos, which could be delivered simultaneously or in tandem ( Zhu et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Endocytosis inhibitors block SARS-CoV-2 pseudoparticle infection of mink lung epithelium

Song,

Phandthong,

Talbot

2023

Front. Microbiol.

View full text Add to dashboard Cite

IntroductionBoth spill over and spill back of SARS-CoV-2 virus have been reported on mink farms in Europe and the United States. Zoonosis is a public health concern as dangerous mutated forms of the virus could be introduced into the human population through spillback.MethodsThe purpose of our study was to determine the SARS-CoV-2 entry mechanism using the mink lung epithelial cell line (Mv1Lu) and to block entry with drug inhibitors.ResultsMv1Lu cells were susceptible to SARS-CoV-2 viral pseudoparticle infection, validating them as a suitable disease model for COVID-19. Inhibitors of TMPRSS2 and of endocytosis, two pathways of viral entry, were tested to identify those that blocked infection. TMPRSS2 inhibitors had minimal impact, which can be explained by the apparent lack of activity of this enzyme in the mink and its localization within the cell, not on the cell surface.DiscussionDyngo4a, a small molecule endocytosis inhibitor, significantly reduced infection, supporting the conclusion that the entry of the SARS-CoV-2 virus into Mv1Lu cells occurs primarily through endocytosis. The small molecule inhibitors that were effective in this study could potentially be used therapeutically to prevent SARS-CoV-2 infection in mink populations. This study will facilitate the development of therapeutics to prevent zoonotic transmission of SARS-CoV-2 variants to other animals, including humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Endocytosis inhibitors block SARS-CoV-2 pseudoparticle infection of mink lung epithelium

Song,

Phandthong,

Talbot

2023

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Calabrese et al [ 139 ] demonstrated that andrographolide administered orally for 3 weeks at a dose of 5 mg/kg body weight, escalating to 10 mg/kg bodyweight for 3 weeks, and to 20 mg/kg bodyweight for a final 3 weeks caused mild to moderate headache, soreness, rash, taste symptoms, diarrhea, or itching anaphylactic reaction. The acute and subacute toxicity of AG-2-HyP-β-CYD complex on SD rats following oral and inhalation routes of administration was recently tested [ 140 ]. The lethal dose (LD 50 ) was found to be > 2000 mg/kg in addition to NOAEL (no observed adverse effect level) of 666 mg/kg.…”

Section: Adverse Effectsmentioning

confidence: 99%

Anti-Cancer Agent: The Labdane Diterpenoid-Andrographolide

Tundis

Patra

Bonesi

et al. 2023

Plants

View full text Add to dashboard Cite

In spite of the progress in treatment strategies, cancer remains a major cause of death worldwide. Therefore, the main challenge should be the early diagnosis of cancer and the design of an optimal therapeutic strategy to increase the patient’s life expectancy as well as the continuation of the search for increasingly active and selective molecules for the treatment of different forms of cancer. In the recent decades, research in the field of natural compounds has increasingly shifted towards advanced and molecular level understandings, thus leading to the development of potent anti-cancer agents. Among them is the diterpene lactone andrographolide, isolated from Andrographis paniculata (Burm.f.) Wall. ex Nees that showed shows a plethora of biological activities, including not only anti-cancer activity, but also anti-inflammatory, anti-viral, anti-bacterial, neuroprotective, hepatoprotective, hypoglycemic, and immunomodulatory properties. Andrographolide has been shown to act as an anti-tumor drug by affecting specific molecular targets that play a part in the development and progression of several cancer types including breast, lung, colon, renal, and cervical cancer, as well as leukemia and hepatocarcinoma. This review comprehensively and systematically summarized the current research on the potential anti-cancer properties of andrographolide highlighting its mechanisms of action, pharmacokinetics, and potential side effects and discussing the future perspectives, challenges, and limitations of use.

show abstract

“…The delivery of Dyngo4a and mβCD via nasal spray directly introduces the drugs to the desired target (respiratory system) in contrast to drugs that are injected or ingested. Given the ability of mβCD to solubilize various drugs, it is currently widely used as an excipient for enhancing drug delivery via nebulization (Evrard et al 2004;Chandrama Singh et al 2022). Nebulization with Dyngo4a and mβCD could also be used in conjunction with other therapies, such as antisense oligos, which could be delivered simultaneously or in tandem (Zhu et al 2022).…”

Section: Administration and Delivery Of Validated Small Molecule Inhi...mentioning

confidence: 99%

Endocytosis Inhibitors Block SARS-CoV-2 Pseudoparticle Infection of Mink Lung Epithelium

Song

Phandthong

Talbot

2023

Preprint

View full text Add to dashboard Cite

Both spill over and spill back of SARS-CoV-2 virus have been reported on mink farms in Europe and the United States. Zoonosis is a public health concern as dangerous mutated forms of the virus could be introduced into the human population through spillback. The purpose of our study was to determine the SARS-CoV-2 entry mechanism using mink lung epithelial cell line (Mv1Lu) and to block entry with drug inhibitors. Mv1Lu cells were susceptible to SARS-CoV-2 viral pseudoparticle infection, validating them as a suitable disease model for COVID-19. Inhibitors of TMPRSS2 and of endocytosis, two pathways of viral entry, were tested to identify those that blocked infection. Dyngo4a, a small molecule endocytosis inhibitor, significantly reduced infection, while TMPRSS2 inhibitors had minimal impact, supporting the conclusion that the entry of the SARS-CoV-2 virus into Mv1Lu cells occurs primarily through endocytosis. The small molecule inhibitors that were effective in this study could potentially be used therapeutically to prevent SARS-CoV-2 infection in mink populations. This study will facilitate the development of therapeutics to prevent zoonotic transmission of SARS-CoV-2 variants to other animals, including humans.

show abstract

Acute and Subacute Toxicity Assessment of Andrographolide-2-hydroxypropyl-β-cyclodextrin Complex via Oral and Inhalation Route of Administration in Sprague-Dawley Rats

Cited by 9 publications

References 35 publications

Endocytosis inhibitors block SARS-CoV-2 pseudoparticle infection of mink lung epithelium

Endocytosis inhibitors block SARS-CoV-2 pseudoparticle infection of mink lung epithelium

Anti-Cancer Agent: The Labdane Diterpenoid-Andrographolide

Endocytosis Inhibitors Block SARS-CoV-2 Pseudoparticle Infection of Mink Lung Epithelium

Contact Info

Product

Resources

About