Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Sci Prog. 2024 Oct-Dec;107(4):368504241296305. doi: 10.1177/00368504241296305.

Development of a rapid method for the simultaneous determination of 
aminophylline, doxofylline, bromhexine, and ambroxol by HPLC.

Meng X(1), Feng Y(1), Chen F(1), Shi M(1), Fang B(1).

Author information:
(1)Department of Pharmacy, Sinopharm Dongfeng General Hospital, Hubei University 
of Medicine, Shiyan, China.

Introduction: Antitussive and expectorant drugs such as aminophylline (APL), 
doxofylline (DXL), bromhexine hydrochloride (BXH), and ambroxol hydrochloride 
(AXH), either individually or in combination, are widely used in the prevention 
and treatment of respiratory diseases. The study aimed to establish a 
high-performance liquid chromatography (HPLC) method for the simultaneous 
determination of these four drugs and to investigate their stability in 0.9% 
sodium chloride injection or 5% glucose injection over 48 hours. Methods: An 
InertSustain C18 column (150 mm × 4.6 mm, 5 μm) was used. The mobile phase 
consisted of acetonitrile and 50 mmol·L-1 potassium dihydrogen phosphate 
solution (pH 4.0) with gradient elution. The flow rate was 0.8 mL·min-1, and the 
column temperature was maintained at 30°C. The stability of APL, DXL, BXH, and 
AXH in 0.9% sodium chloride and 5% glucose injections over 48 h was determined 
using HPLC. Results: APL, DXL, BXH, and AXH showed good linearity within the 
ranges of 0.01 to 0.20, 0.003-0.06, 0.015-0.30, and 0.016-0.16 mg·mL-1, 
respectively (r > 0.999). The intraday and interday relative standard deviations 
were <2%, with recovery rates between 98.4% and 102.2%. The four drugs remained 
colorless and clear in infusion mixtures. The pH value fluctuated within ±0.3 
over 48 hours, and the relative percentage content of the drugs ranged from 
95.0% to 105.0%. Conclusion: The established HPLC method is simple, reliable, 
and stable, allowing for the simultaneous determination of the four antitussive 
and expectorant drugs. APL, DXL, BXH, and AXH were stable within 48 hours when 
mixed with 0.9% sodium chloride and 5% glucose injections.

DOI: 10.1177/00368504241296305
PMCID: PMC11536682
PMID: 39492710 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of conflicting interestsThe authors 
declared no potential conflicts of interest with respect to the research, 
authorship, and/or publication of this article.


2. Bratisl Lek Listy. 2024;125(11):713-718. doi: 10.4149/BLL_2024_108.

Theophylline in the prevention of vasovagal syncope recurrences.

Mitro P, Lazurova Z, Lukacova M.

OBJECTIVES: The present work aimed to study the efficacy and patient compliance 
of oral theophylline treatment in the prevention of vasovagal syncope 
recurrences.
BACKGROUND: High blood adenosine may trigger vasovagal syncope. Theophylline is 
an adenosine receptor antagonist.
METHODS: In 44 patients with vasovagal syncope (8 men and 34 women, age 46.4±3.2 
years) with an average 4.8±0.74 syncopal episodes (range 1-20, median 4,5 
episodes) oral theophylline therapy was started with dose 2x100/200 mg, which 
was further increased if necessary. All patients were treated by 
non-pharmacological measures which were not effective. Patients were followed in 
regular intervals on an outpatient basis in 6-month intervals.
RESULTS: After the start of treatment patients were followed for the mean of 
17.1±2.1 months (2-51 months, median 12 months). The total number of syncopal 
episodes decreased from 4.8±0.74 to 1.73±0.45 (p=0.0006). The occurrence of 
syncopal episodes per year decreased from 4.07±0.80/year to 1.50±0.54 /year 
during the treatment period (p=0.001). After a gradual increase in theophylline 
dosage, in 34 patients no syncopal recurrences were observed. In 10 persons 
syncopal recurrences persisted despite treatment. Side effects leading to 
discontinuation of treatment were present in 14 patients - gastrointestinal 
intolerance (7 patients), palpitations (6 patients) and headache (3 patients).
CONCLUSION: The addition of oral theophylline preparation to non-pharmacological 
treatment led to a marked reduction of syncopal recurrence in patients with 
vasovagal syncope. About one-third of study subjects discontinued therapy 
because of side effects (Tab. 2, Fig. 4, Ref. 22). Text in PDF www.elis.sk 
Keywords: heophylline, adenosine, vasovagal syncope, treatment.

DOI: 10.4149/BLL_2024_108
PMID: 39487841 [Indexed for MEDLINE]


3. Food Chem. 2024 Oct 28;464(Pt 2):141818. doi: 10.1016/j.foodchem.2024.141818. 
Online ahead of print.

Metabolic function and quality contribution of tea-derived microbes, and their 
safety risk in dark tea manufacture.

Cheng L(1), Peng L(1), Xu L(1), Yu X(2), Zhu Y(2), Wei X(3).

Author information:
(1)School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 
200240, PR China.
(2)Hubei Qingzhuan Tea Industry Development Group Co. Ltd., Xianning 437000, PR 
China.
(3)School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 
200240, PR China. Electronic address: foodlab2010@163.com.

Microbial fermentation, especially the microbes involved, plays a crucial role 
in the quality formation of dark tea. Over the last decade, numerous microbes 
have been isolated from dark tea and in turn, applied to dark tea manufacture 
through pure-strain, mixed-strain, and enhanced fermentation. This article 
systematically summarizes the specific metabolic function and quality 
contribution of tea-derived microbes, with special attention paid to their 
safety risk. Aspergillus niger converts catechins via hydrolysis, addition, 
oxidative polymerization, and B-ring fission, contributing greatly to the 
reddish-brown color and mellow taste of dark tea. Aspergillus sydowii and 
Penicillium simplicissimum are caffeine-degrading microbes, degrading caffeine 
mainly into theophylline. However, under adverse conditions, Aspergillus, 
Penicillium, and Fusarium species potentially produce aflatoxins, ochratoxin A, 
and citrinin, the mycotoxins occurring in dark tea. The in-depth knowledge of 
tea-derived microbes is important for improving the quality and safety of dark 
tea, providing a theoretical basis for its industrial modernization.

Copyright © 2024. Published by Elsevier Ltd.

DOI: 10.1016/j.foodchem.2024.141818
PMID: 39486219

Conflict of interest statement: Declaration of competing interest The authors 
declare that they have no known competing financial interests or personal 
relationships that could have appeared to influence the work reported in this 
paper.


4. Pharmaceutics. 2024 Oct 18;16(10):1335. doi: 10.3390/pharmaceutics16101335.

The Key Role of Wettability and Boundary Layer in Dissolution Rate Test.

Biasin A(1), Pribac F(1), Franceschinis E(2), Cortesi A(1), Grassi L(1), 
Voinovich D(3), Colombo I(1), Grassi G(4), Milcovich G(5)(6), Grassi M(1), 
Abrami M(1).

Author information:
(1)Department of Engineering and Architecture, University of Trieste, Via 
Valerio 6/A, I-34127 Trieste, Italy.
(2)Department of Pharmaceutical and Pharmacological Sciences, University of 
Padova, Via Marzolo 5, I-35131 Padova, Italy.
(3)Department of Chemical and Pharmaceutical Sciences, University of Trieste, 
Via Giorgeri 1, I-34127 Trieste, Italy.
(4)Clinical Department of Medical, Surgical and Health Sciences, Cattinara 
University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, 
Italy.
(5)Department of Biological, Chemical and Pharmaceutical Sciences and 
Technologies, University of Palermo, I-90128 Palermo, Italy.
(6)Department of Life Sciences, University of Modena and Reggio Emilia, I-41125 
Modena, Italy.

BACKGROUND/OBJECTIVES: The present work proposes a mathematical model able to 
describe the dissolution of poly-disperse drug spherical particles in a solution 
(Dissolution Rate Test-DRT). DRT is a pivotal test performed in the 
pharmaceutical field to qualitatively assess drug bioavailability.
METHODS: The proposed mathematical model relies on the key hallmarks of DRT, 
such as particle size distribution, solubility, wettability, hydrodynamic 
conditions in the dissolving liquid of finite dimensions, and possible 
re-crystallization during the dissolution process. The spherical shape of the 
drug particles was the only cue simplification applied. Two model drugs were 
considered to check model robustness: theophylline (both soluble and wettable) 
and praziquantel (both poorly soluble and wettable).
RESULTS: The DRT data analysis within the proposed model allows us to understand 
that for theophylline, the main resistance to dissolution is due to the boundary 
layer surrounding drug particles, whereas wettability plays a negligible role. 
Conversely, the effect of low wettability cannot be neglected for praziquantel. 
These results are validated by the determination of drug wettability performed 
while measuring the solid-liquid contact angle on four liquids with decreasing 
polarities. Moreover, the percentage of drug polarity was determined.
CONCLUSIONS: The proposed mathematical model confirms the importance of the 
different physical phenomena leading the dissolution of poly-disperse solid drug 
particles in a solution. Although a comprehensive mathematical model was 
proposed and applied, the DRT data of theophylline and praziquantel was 
successfully fitted by means of just two fitting parameters.

DOI: 10.3390/pharmaceutics16101335
PMCID: PMC11511008
PMID: 39458664

Conflict of interest statement: The authors declare no conflicts of interest.


5. Int J Biol Sci. 2024 Sep 30;20(13):5312-5329. doi: 10.7150/ijbs.99936. 
eCollection 2024.

Theophylline derivatives promote primordial follicle activation via 
cAMP-PI3K/Akt pathway and ameliorate fertility deficits in naturally aged mice.

Zhang W(1), Gao L(1), Zhang X(1), Weng Y(1), Du Y(1), Sun YL(1), Wei H(1), Hao 
T(1), Chen Y(2), Liang X(3), Zhang M(1).

Author information:
(1)The Innovation Centre of Ministry of Education for Development and Diseases, 
The Second Affiliated Hospital, School of Medicine, South China University of 
Technology, Guangzhou, Guangdong, 510006, China.
(2)Reproductive Medicine Center, Zhongshan City People's Hospital, Zhongshan, 
Guangdong, 528403, China.
(3)Reproductive Medicine Research Center, The Sixth Affiliated Hospital of Sun 
Yat-sen University, Guangzhou, Guangdong, 510655, China.

In elderly women and patients with premature ovarian insufficiency (POI), 
activating their remaining dormant primordial follicles in vivo is challenging. 
In this study, we found that phosphodiesterase (PDE) subtypes were expressed 
mainly in primordial follicle oocytes. The specific PDE inhibitors and 
theophylline derivatives (aminophylline, dyphylline, and enprofylline) activated 
primordial follicles in neonatal mice by ovary culture and intraperitoneal 
injection. These inhibitors also increased the levels of ovarian cyclic 
adenosine monophosphate (cAMP) and oocyte phosphorylated protein kinase B 
(p-Akt). The blockade of gap junctions using carbenoxolone (CBX) increased the 
levels of ovarian cAMP and pre-granulosa cell phosphorylated mammalian target of 
rapamycin (p-mTOR), suggesting that oocyte PDEs hydrolyze cAMP from 
pre-granulosa cells through gap junctions to maintain primordial follicle 
dormancy. Importantly, oral aminophylline improved ovulated oocyte quantity and 
quality, and increased offspring numbers in naturally aged mice. In addition, 
theophylline derivatives also activated human primordial follicles and increased 
p-Akt levels. Thus, theophylline derivatives activate primordial follicles by 
accumulating cAMP levels and activating phosphatidylinositol 3-kinase (PI3K)/Akt 
pathway in oocytes, and oral aminophylline increased fertility in naturally aged 
female mice by improving ovulated oocyte quantity and quality. As oral 
medications, theophylline derivatives may be used to improve fertility in 
elderly women and patients with POI.

© The author(s).

DOI: 10.7150/ijbs.99936
PMCID: PMC11489179
PMID: 39430241 [Indexed for MEDLINE]

Conflict of interest statement: Competing Interests: The authors have declared 
that no competing interest exists.