Pterodontic acid Isolated from Laggera pterodonta Inhibits Dengue Virus Serotype 2 Infection

Research Article

Austin Med Sci. 2019; 4(1): 1032.

Pterodontic acid Isolated from Laggera pterodonta Inhibits Dengue Virus Serotype 2 Infection

Qin L1,2†, Li W1,3†, Zhang L1, Wang X4, Wang Y4, Yu H1*, Hu W1* and Zhang R1*

1School of Pharmaceutical Science, Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, China

2First Affiliated Hospital of Kunming Medical University, China

3Third Hospital of Yunnan Province, China

4State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, (Guangzhou Medical University), China

*Corresponding author: Yu H, Hu W and Zhang R, School of Pharmaceutical Science, Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650000, China

†These authors contributed equally to this work

Received: June 06, 2019; Accepted: July 17, 2019; Published: July 24, 2019


Dengue is the most important arbovirus disease in the world in terms of the highest morbidity and mortality. Unfortunately, there is no specific medication for it so far. In the present study, we investigated the anti-DENV-2 activity of Pterodontic acid, isolated from Laggera pterodonta. Pterodontic acid was found to have strong activity in vitro against DENV-2 with low cytotoxicity. These findings suggest that Pterodontic acid has the potential to be developed into an anti-virus drug for the prevention and treatment of DENV-2 virus infection.

Keywords: Laggera pterodonta; pterodontic acid; Dengue virus serotype 2; Antiviral activity; Sesquiterpenes


CCL-5: Chemokine (C-C motif) ligand 5; CPE: cytopathic effect; Denv-2: dengue virus serotype 2; DF: dengue fever; DHF: dengue hemorrhagic fever; DHTMF: 3, 5-Dihydroxy-6, 7, 3'4'-tetramethoxyflavone; DSS: dengue shock syndrome; HSV-I: herpes simplex type I; HSV-II: herpes simplex type II; L. pterodonta: Laggera pterodonta; NF-κB: Nuclear factor-κB; RSV: respiratory syncytial virus; RT-qPCR: Reverse transcription-quantitative polymerase chain reaction; TCM: Traditional Chinese medicine; TFLP: total flavonoids of L. pterodonta; TNF-a: tumor necrosis factor alpha; TPLP: total phenolics from L. pterodonta


The dengue virus (DENV) is transmitted between human beings and primarily Aedes aegypti mosquitoes [1]. Dengue virus (DENV) is endemic in tropical and sub-tropical regions of the world [2]. An estimated 390 million people are infected annually, of which 96 million cases are symptomatic but fewer than 1% of cases are fatal [2- 4]. Most clinically apparent infections result in a self-limiting febrile illness called ‘dengue fever’. However, a minority of patients develop dengue hemorrhagic fever–dengue shock syndrome, a more serious manifestation characterized by vascular leakage and circulatory failure [5]. There are four serotypes of DENV (DENV1–DENV4), which differ at the amino-acid level by 30–35% [5]. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection [6]. No specific treatment exists for dengue fever, and vector control has been largely ineffective at preventing the rapid geographic spread of the disease [7- 9]. Therefore, it is necessary to develop an innovative antiviral drug.

Traditional Chinese medicine (TCM) is widely used in China to treat viral disease. TCM is considered to be safe, effective and multi-targeted [10]. Numerous medicinal plants exhibit antiviral activity through different mechanisms and these may lead to the development of novel antiviral drugs [10].

Laggera pterodonta (DC.) Benth. (Compositae) is a perennial herb widely distributed in southwest China, especially in Yunnan province [11]. Certain antiviral compounds have been isolated from L. pterodonta, including flavonoids, which have an anti-inflammatory and anti-apoptotic effect, in addition to three dicaffeoylquinic acids that display antiviral activity against herpes simplex virus-1, herpes simplex virus-2 and influenza A in vitro [10]. The sesquiterpene fraction of L. pterodonta had an anti-influenza virus effect.

Pterodontic acid is one of the main sesquiterpenoids from L. pterodonta, which showed selective anti-viral activities to H1 subtype of human influenza A virus [11], its effect on DENV-2 has not been reported before. In this study, the antivirus activity of pterodontic acid is evaluated using cytopathic effect (CPE) reduction assay and RTPCR.

Materials and Methods

Plant material and preparation of pterodontic acid

The whole herb of Laggera pterodonta, a traditional herbal medicine with the Chinese name Chou Ling Dan, was collected from Yunnan province of China. The herbarium specimen was authenticated by Professor Rongping Zhang and deposited in the College of Pharmaceutical Sciences, Kunming Medical University.

The powdered plant material (1 kg) was extracted with methanol using a percolation process, followed by collecting a 40 L elution and vacuum-concentrating to yield a 135 g methanol extract. The extract was suspended in H2O (800 mL) and subjected to liquid– liquid partition by adding petroleum ether. The residue (48 g) of the petroleum ether layer was subjected to silica gel CC (petroleum ether–EtOAc, 10:1) to obtain fraction A (38 g). Fraction A (8 g) was subjected to silica gel CC with elution by a gradient of petroleum ether–EtOAc (1:0; 20:1; 10:1; 5:1; 2:1) to yield fractions 1–12 based on TLC analysis. Fr.1 (3.8 g) was the petroleum ether elution and main elution of Fraction A. Fr.1 was further subjected to silica gel CC (petroleum ether–CHCl3, from 100:0 to 95:5) to obtain five fractions (I–V) for TLC analysis, Fr.III was further purified by gel CC to afford a compound (34.7 mg) with purity higher than 95%, which was identified as pterodontic acid (Figure1).