A placebo-controlled, double-blinded, randomized, dose-finding trial using a combination of apocynin and paeonol (APPA) for the treatment of knee osteoarthritis

Start Date16 Jul 2024

Sponsor / Collaborator

AKL Research & Development Ltd.

EUCTR2020-000249-14-DK / Not yet recruitingPhase 2

A placebo-controlled, double-blinded, randomized, trial using a combination of apocynin and paeonol (APPA) for the treatment of knee osteoarthritis

Start Date19 Aug 2020

Sponsor / Collaborator

AKL Research & Development Ltd.

IRCT20200418047122N1 / RecruitingPhase 2/3IIT

Evaluation of the protective effect of a combination drug including Apocynin, Niacin, and Tannin on prevention of cardiovascular and respiratory morbidities and mortality in COVID-19 infection: A Clinical Trial

Start Date25 Apr 2020

Sponsor / Collaborator

Isfahan University of Medical Sciences

100 Clinical Results associated with Apocyanin

100 Translational Medicine associated with Apocyanin

100 Patents (Medical) associated with Apocyanin

2,373

Literatures (Medical) associated with Apocyanin

01 Feb 2025·Food Chemistry

Integrated targeted and untargeted metabolomics profiling of Vanilla species from the Atlantic Forest: Unveiling the bioeconomic potential of Vanilla cribbiana

Article

Author: Koblitz, Maria Gabriela Bello ; da Silva Oliveira, Joana Paula ; Garrett, Rafael ; Macedo, Andrea Furtado

In this study, we employ both targeted and untargeted approaches to explore the metabolomic profiles of Vanilla spp., with a particular focus on V. cribbiana (VCR) and its comparison with V. planifolia (VP). We also examine V. bahiana and V. chamissonis using targeted approaches. Through advanced analytical techniques, our untargeted LC-HRMS approach led to the annotation of 60 metabolites, revealing a complex chemical composition with 34 novel compounds in the Vanilla genus in VCR and VP. These findings highlight significant flavoring compounds and lay the foundation for a subsequent quantitative estimation approach. Our targeted analysis, which measured key molecules, underscores VCR's potential in producing vanillin and acetovanillone at levels comparable to the commercially valuable VP and even higher levels of vanillic acid. This research enriches our understanding of flavor composition in vanilla species and emphasizes the importance of exploring wild relatives of vanilla crop for sustainable production and biodiversity conservation.

01 Dec 2024·Molecular and Cellular Endocrinology

Paricalcitol prevents renal tubular injury induced by ischemia-reperfusion: Role of oxidative stress, inflammation and AT1R

Article

Author: Ribeiro, Fernanda Priscila Barbosa ; Carvalho, Jennyfer Martins de ; Santos, Valéria Bianca de Souza ; Siqueira, Lucas Cristiano da Silva ; Silva, Jeoadã Karollyne ; Gomes, José Anderson da Silva ; Albuquerque, Jéssica Santos Schirato ; Lima, Natália Kryzia Dos Santos ; Vieira, Leucio Duarte ; Tenorio, Fernanda das Chagas Angelo Mendes ; Cirilo, Marry Aneyts de Santana ; Lima, Natália Kryzia dos Santos

The vitamin D receptor (VDR) is associated with antioxidative and anti-inflammatory effects and modulation of the renin-angiotensin-aldosterone system. This study evaluated whether VDR agonist paricalcitol protects renal ischemia-reperfusion (IR) induced tubular injury in rats by evaluating: 1) ATP-dependent tubular Na⁺ transport; 2) renal redox signaling; 3) renal content of proinflammatory cytokines TNF-α and IL-6; and 4) renal content of renin and angiotensin II receptor type 1 (AT₁R). Paricalcitol prevented IR-induced tubular injury, evidenced by the prevention of histopathological changes and renal fibrosis with preservation of the activity of ATP-dependent Na⁺ transporters in the renal cortex. Paricalcitol decreased renal oxidative stress by reducing NADPH oxidase activity and increasing catalase. Paricalcitol also decreased the renal content of TNF-α, IL-6, and AT₁R. The NADPH oxidase inhibitor apocynin did not present additive protection to paricalcitol-induced effects. The protective effects of paricalcitol on tubular injury induced by renal IR may dependent on the modulation of redox and proinflammatory signaling and renal angiotensin II/AT₁R signaling.

01 Nov 2024·Naunyn-Schmiedeberg's Archives of Pharmacology

Molecular mechanisms underlying methotrexate-induced intestinal injury and protective strategies

Review

Author: Hassanein, Emad H M ; Ali, Gaber F ; Mohamed, Wafaa R

AbstractMethotrexate (MTX) is a folic acid reductase inhibitor that manages various malignancies as well as immune-mediated inflammatory chronic diseases. Despite being frequently prescribed, MTX’s severe multiple toxicities can occasionally limit its therapeutic potential. Intestinal toxicity is a severe adverse effect associated with the administration of MTX, and patients are significantly burdened by MTX-provoked intestinal mucositis. However, the mechanism of such intestinal toxicity is not entirely understood, mechanistic studies demonstrated oxidative stress and inflammatory reactions as key factors that lead to the development of MTX-induced intestinal injury. Besides, MTX causes intestinal cells to express pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which activate nuclear factor-kappa B (NF-κB). This is followed by the activation of the Janus kinase/signal transducer and activator of the transcription3 (JAK/STAT3) signaling pathway. Moreover, because of its dual anti-inflammatory and antioxidative properties, nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) has been considered a critical signaling pathway that counteracts oxidative stress in MTX-induced intestinal injury. Several agents have potential protective effects in counteracting MTX-provoked intestinal injury such as omega-3 polyunsaturated fatty acids, taurine, umbelliferone, vinpocetine, perindopril, rutin, hesperidin, lycopene, quercetin, apocynin, lactobacillus, berberine, zinc, and nifuroxazide. This review aims to summarize the potential redox molecular mechanisms of MTX-induced intestinal injury and how they can be alleviated. In conclusion, studying these molecular pathways might open the way for early alleviation of the intestinal damage and the development of various agent plans to attenuate MTX-mediated intestinal injury.Graphical Abstract

News (Medical) associated with Apocyanin

16 Jan 2024

·www.pharmaceutical-technology.com

Allakos cuts employee count by half after two Phase II failures

Allakos is halting all lirentelimab-related activities and axing half of its workforce. Credit: Pavel Kapysh via Shutterstock. US-based biotech Allakos has announced that two Phase II clinical trials for atopic dermatitis and chronic spontaneous urticaria with its lead drug lirentelimab failed to meet their primary endpoints. Free Report How is the Biopharmaceutical industry evolving? 2021 was a year of continued innovation and change in the Biopharmaceutical industry. As the COVID-19 pandemic continues to take its toll on businesses worldwide, it’s time to look for new ways to create value, prepare for the future, and remain competitive in the ever-changing landscape. GlobalData’s expansive report examines the business environment and trends that shape the Biopharmaceutical industry. We highlight the most impactful emerging technologies, as well as the industry, regulatory, and macroeconomic factors that influence growth prospects. Access the report to: Benchmark the impact of major themes on the Biopharmaceutical industry. Gain a deeper "on the ground" perspective through exclusive opinions and analysis from industry respondents. Evaluate the effects of COVID-19 on the sector. Download the full report to understand what to expect and how to align your strategies for success. 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Our services are intended for corporate subscribers and you warrant that the email address submitted is your corporate email address. Thank you. You will recieve your mail in sometime.So, please check your email to download the Report. Go deeper with GlobalData Reports LOA and PTSR Model - (Apocynin + Paeonol) in Osteoarthritis Reports LOA and PTSR Model - Alpelisib in Mutational Disorders Premium Insights The gold standard of business intelligence. Find out more Related Company Profiles Allakos Inc View all In the Phase II ATLAS trial (NCT05155085) assessing lirentelimab for patients with atopic dermatitis, the primary endpoint – measuring the proportion of patients achieving a 75% reduction from baseline in Eczema Area and Severity Index (EASI-75) – did not achieve statistical significance, with 23% of patients treated with lirentelimab achieving EASI-75 compared to 18% of patients in the placebo group. The primary endpoint also fell short in the Phase IIb MAVERICK trial (NCT05528861) assessing patients with chronic spontaneous urticaria, with those in the lirentelimab group experiencing a change of -27% in urticaria activity score (UAS7), compared to a change of -26% in the placebo group. In response to these results, Allakos said it is initiating a workforce reduction of approximately 50% to reduce costs and ensure an extended cash runway. Additionally, the company will now also halt all lirentilimab-related activities. Allakos’ stock has plunged 59% after announcing the results on 16 January, compared to the price on the previous trading day of 12 January. Allakos will now concentrate its efforts on AK006, a humanised IgG1 monoclonal antibody candidate. An ongoing Phase I study for AK006 in healthy volunteers is set to progress, with the completion of its single and multiple ascending dose cohorts expected by Q1 2024. While lirentelimab targeted Siglec-8, which is found on mast cells and eosinophils, AK002 is an agonist of Siglec-6, which is exclusively expressed on mature mast cells. Mast cells and eosinophils are types of immune cells, and are studied to understand a drug’s activity. In the ATLAS study, blood eosinophil counts of lirentelimab-treated patients decreased by 96% compared to 15% for those on placebo. The San Carlos, California-headquartered company plans to launch a Phase I trial for intravenous AK006 in chronic spontaneous urticaria in Q2 2024, anticipating topline data by the end of the year. In the announcement accompanying the results, chief medical officer of Allakos Craig Paterson said: “We are disappointed that these trials did not meet their primary endpoint, particularly given the need for new treatment options for patients with these severe diseases. Given that neither trial met its primary endpoint, we have decided to not pursue further clinical development of lirentelimab.” Free Report How is the Biopharmaceutical industry evolving? 2021 was a year of continued innovation and change in the Biopharmaceutical industry. As the COVID-19 pandemic continues to take its toll on businesses worldwide, it’s time to look for new ways to create value, prepare for the future, and remain competitive in the ever-changing landscape. GlobalData’s expansive report examines the business environment and trends that shape the Biopharmaceutical industry. We highlight the most impactful emerging technologies, as well as the industry, regulatory, and macroeconomic factors that influence growth prospects. Access the report to: Benchmark the impact of major themes on the Biopharmaceutical industry. Gain a deeper "on the ground" perspective through exclusive opinions and analysis from industry respondents. Evaluate the effects of COVID-19 on the sector. Download the full report to understand what to expect and how to align your strategies for success. 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Our services are intended for corporate subscribers and you warrant that the email address submitted is your corporate email address. Thank you. You will recieve your mail in sometime.So, please check your email to download the Report.

Clinical ResultPhase 2Phase 1

20 Mar 2023

·www.biospace.com

New data by AKL Therapeutics suggests investigational oral osteoarthritis drug APPA may have a promising senotherapeutic effect with potential in other diseases of ageing

New data* presented at the 2023 Osteoarthritis Research Society International (OARSI) World Congress in Denver, Colorado (March 17th-20th) suggest that AKL Therapeutics' investigational oral osteoarthritis (OA) drug APPA** may have a dual effect on senescence1 – a process in which cells stop dividing as a natural consequence of ageing.2 Senescence plays a major role in the development of many age-related diseases, including osteoarthritis (OA).3 The study, using a human chondrocyte (cartilage-forming) cell line, was carried out at the Institute of Biomedical Research of A Coruña (INIBIC) in Spain.1 It found that APPA appears to not only reduce the number of harmful senescent cells which build up in the cartilage causing inflammation (a 'senolytic' effect), but could also potentially reverse the senescence process so cells can function normally again (a 'senomorphic' effect).1,4 The study found that APPA significantly reduced the number of senescent cells (p=0.020) and increased the number of cells - indicated by the number of nuclei (p=0.062) - in the chondrocyte cell line in which senescence had been induced.1 Alan Reynolds, Chief Scientific Officer at AKL Therapeutics, says: "These latest findings raise the tantalising possibility that APPA could modify the progression of debilitating OA for patients by eliminating or delaying the adverse effects of cellular senescence and the process of ageing.3 "Frailty and mobility issues have a significant impact as we age, often leading to people living many years in pain and ill health.5,6 If we can reduce senescence, which contributes to joint damage in OA7 and is involved in many other age-related diseases, we can hopefully help improve peoples' healthspan, so they age in better physical and mental health."8 As we age, dysfunctional senescent cells – often dubbed "zombie" cells – build up in the body while secreting harmful chemicals which cause inflammation and damage surrounding tissue – a process known as senescence.2 They have become one of the most promising targets for healthy ageing research as senescence is now known to play a major role in the development of many age-related diseases, including OA, Chronic Obstructive Pulmonary Disease (COPD), Alzheimer's Disease, Parkinson's Disease, osteoporosis, and diabetes.9 Developing a new class of drugs called senotherapeutics to eliminate or delay the damaging effects of this cellular senescence is a new frontier in medicine.10 Senotherapeutics have the potential to increase healthspan by delaying the worse effects of ageing, which would reduce the burden of age-related diseases and could save healthcare systems billions every year.11 David Miles, Chief Executive Officer at AKL Therapeutics, says: "With a unique mechanism of action,12-15 APPA is the only oral drug that targets the multiple signalling pathways in bone, cartilage and inflammation involved in OA, delivering pain relief to multiple joints. With this latest data now showing that APPA has a potential senomorphic effect, we've recently filed a patent application and will look to carry out further studies on other senescence-related diseases to investigate its potential as a senotherapeutic." APPA is an oral, patented, fixed-dose combination of two synthetically produced, synergistic, secondary metabolites of plant origin.16,17 Previous human clinical trials have shown that APPA has a good safety profile, is well-tolerated and reduces pain in OA.18,19 Importantly, it has been shown to reduce levels of cartilage-damaging enzymes and levels of bone destruction.13-15 The Phase 2a trial found that those with more severe disease benefited most from APPA with a statistically significant improvement in pain vs placebo.18 AKL is now raising funding for a Phase 2b trial of APPA as a potential treatment for patients with more severe OA - the largest patient group which also has the highest unmet need.20 AKL was granted an Innovation Passport for APPA in 2021 by the UK's Medicines and Healthcare products Regulatory Agency (MHRA) which sets out an accelerated roadmap of future development and regulatory milestones.21 There are currently no effective and well tolerated oral therapies that provide long-term pain relief or reduce the progression of OA, a common, debilitating, degenerative disease of the joints involving the cartilage, bone, and its surrounding tissues.22 OA is the most common joint disease worldwide, affecting an estimated 10% of men and 18% of women over 60 years of age.23 Globally, the prevalent cases of OA increased by 113.25%, from 247.51 million in 1990 to 527.81 million in 2019, with OA of the knee contributing most to the overall burden.24 REFERENCES: 1. Fernandez-Moreno M, Hermida Gómez T, Larkins N, Reynolds A, Blanco-Garcia F. Effect of APPA (combination of apocynin and paeonol) compound on cellular senescence using human articular chondrocytes. Osteoarthritis and Cartilage. 2023; 31 (Supplement 1):S401-402 Abstract 447. 2. Lagoumtzi SM, Chondrogianni N. Senolytics and senomorphics: Natural and synthetic therapeutics in the treatment of aging and chronic diseases. Free Radic Biol Med. 2021 Aug 1; 171:169-190. 3. Coryell PR, Diekman BO, Loeser RF. Mechanisms and therapeutic implications of cellular senescence in osteoarthritis. Nature reviews Rheumatology. 2021 Jan; 17(1):47-57. 4. Zhang L, Pitcher LE, Prahalad V, Niedernhofer LJ, Robbins PD. Targeting cellular senescence with senotherapeutics: senolytics and senomorphics. FEBS J. 2023 Mar; 290(5):1362-1383. 5. Howlett SE, Rutenberg AD, Rockwood K. The degree of frailty as a translational measure of health in aging. Nature Aging. 2021 2021/08/01; 1(8):651-665. 6. Kojima G, Liljas AEM, Iliffe S. Frailty syndrome: implications and challenges for health care policy. Risk Manag Healthc Policy. 2019; 12:23-30. 7. Collins JA, Diekman BO, Loeser RF. Targeting aging for disease modification in osteoarthritis. Current opinion in rheumatology. 2018 Jan; 30(1):101-107. 8. McHugh D, Gil J. Senescence and aging: Causes, consequences, and therapeutic avenues. J Cell Biol. 2018 Jan 2; 217(1):65-77. 9. Cellular Senescence in Disease: Academic Press, 2021. 10. Benhamu B, Martin-Fontecha M, Vazquez-Villa H, Lopez-Rodriguez ML, Ortega-Gutierrez S. New Trends in Aging Drug Discovery. Biomedicines. 2022 Aug 18; 10(8). 11. Scott AJ, Ellison M, Sinclair DA. The economic value of targeting aging. Nature Aging. 2021 2021/07/01; 1(7):616-623. 12. Cross AL, Hawkes J, Wright HL, Moots RJ, Edwards SW. APPA (apocynin and paeonol) modulates pathological aspects of human neutrophil function, without supressing antimicrobial ability, and inhibits TNFα expression and signalling. Inflammopharmacology. 2020 Oct; 28(5):1223-1235. 13. Fernandez-Moreno M, Larkins N, Reynolds A, Hermida Gómez T, Blanco FJ. APPA (apocynin and paeonol) reduces ROS production and senescence in human articular chondrocytes. Annals of the rheumatic diseases. 2021; 80(Suppl 1):1051 Abstract AB0036. 14. Fernandez-Moreno M, Larkins N, Reynolds A, Hermida-Gomez T, Blanco FJ. Biological effect of APPA (Apocynin and Paeonol) in human articular chondrocytes. Osteoarthritis and Cartilage. 2021; 29 (supplement1):S358 Abstract 432. 15. Thudium CS, Bay-Jensen AC, Gantzel T, Dziegiel M, Larkins N, Reynolds A. Characterizing the effect of APPA on tissue turnover in cartilage and bonetissue cultures. Osteoarthritis and Cartilage. 2021; 29 (Supplement1):SS152 Abstract 183. 16. Savla SR, Laddha AP, Kulkarni YA. Pharmacology of apocynin: a natural acetophenone. Drug Metab Rev. 2021 Mar 10:1-21. 17. Wu M, Gu Z. Screening of bioactive compounds from moutan cortex and their anti-inflammatory activities in rat synoviocytes. Evid Based Complement Alternat Med. 2009 Mar; 6(1):57-63. 18. Bihlet AR, Byrjalsen I, Andersen JR, Metnik A, Reynolds A, Larkins N, et al. The efficacy and safety of a fixed-dose combination of apocynin and paeonol in symptomatic knee oa: A double-blind, randomized, placebo-controlled clinical trial. Annals of the rheumatic diseases. 2022; 81(Suppl 1):321 Abstract POS0180. 19. Larkins N. Efficacy and safety of the combination of apocynin and paeonol (APPA): an uncontrolled named patient case series. Data on file. 2019. 20. Conaghan PG, Peloso PM, Everett SV, Rajagopalan S, Black CM, Mavros P, et al. Inadequate pain relief and large functional loss among patients with knee osteoarthritis: evidence from a prospective multinational longitudinal study of osteoarthritis real-world therapies. Rheumatology (Oxford, England). 2015 Feb; 54(2):270-277. 21. MHRA awards Innovation Passport for APPA in Osteoarthritis. AKL Therapeutics. [Accessed 16 March 2023] 22. Grässel S, Muschter D. Recent advances in the treatment of osteoarthritis. F1000Res. 2020; 9. 23. Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, et al. Osteoarthritis. Lancet (London, England). 2015 Jul 25; 386(9991):376-387. 24. Long H, Liu Q, Yin H, Wang K, Diao N, Zhang Y, et al. Prevalence Trends of Site-Specific Osteoarthritis From 1990 to 2019: Findings From the Global Burden of Disease Study 2019. Arthritis & rheumatology (Hoboken, NJ). 2022 Jul; 74(7):1172-1183. Date of preparation: March 2023 * Available on request. **Please note: APPA is an investigational medicine and not yet approved for use. View original content: SOURCE AKL Therapeutics

Clinical Study

100 Deals associated with Apocyanin

External Link

KEGG	Wiki	ATC	Drug Bank
-	Apocyanin	-	DB12618

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Atherosclerosis	Phase 1	-	-	-
Diabetic Neuropathies	Preclinical	-	-	-
Hypertension	Preclinical	-	-	-
Inflammatory Bowel Diseases	Preclinical	-	-	-
Parkinson Disease	Preclinical	-	-	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EULAR2024	Not Applicable	-	-	APPA	htgwbzeitq(gvjtiwlpsg) = fmtplanriy cnwzcremay (ephduycxpn )	Positive	05 Jun 2024
				Apocynin	frqxisoaau(lzaglclrdz) = opqpsutdln lucbnfrtay (yibejvavxs ) View more
EULAR2020	Not Applicable	Osteoarthritis	-	Apocynin and paeonol (APPA)	(fjnzsmsbdd) = zxikxrgvjp womoprowso (quzdelxrcp )	Positive	03 Jun 2020
ERS2011	Not Applicable	-	-	Apocynin	qphmgzntwn(mzddafedva) = yqrcbjnygy qkwealqvxy (hdmsvixsjl ) View more	-	01 Sep 2011
LSC 2011 (ERS2011)	Not Applicable	Asthma	14	Apocynin	cdplpqvlzn(kszwtlmgyh) = ywkkvvlcqb ktkspcvgaf (aqevumrpvr ) View more	Positive	01 Sep 2011
				Placebo	cdplpqvlzn(kszwtlmgyh) = ddmschrcxv ktkspcvgaf (aqevumrpvr ) View more
ERS2011	Not Applicable	-	-	Apocynin	dbfgziqqby(dsfgmxtmll) = onztqznqtq fwlokzoubo (fffapqixrc ) View more	-	01 Sep 2011
				Placebo	dbfgziqqby(dsfgmxtmll) = ngjetexujo fwlokzoubo (fffapqixrc ) View more

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