Progress in the Study of Chemical Ingredients and Pharmacological Activities of Shuanghuanglian Preparations: A Review

Abstract

This study integrates the chemical components and pharmacological effects of the three medicinal herbs in Shuanghuanglian preparations—Flos Lonicerae, Radix Scutellariae, and Fructus Forsythiae. Network pharmacology was used to predict action targets associated with antibacterial, anti-inflammatory, and antiviral activities. The results show that Flos Lonicerae mainly contains flavonoids and organic acids. Radix Scutellariae is primarily composed of flavonoids and phenylpropanoids. Fructus Forsythiae includes phenolic acids, lignans, and other compounds. In terms of pharmacological effects, chlorogenic acid and baicalin are the core antibacterial components. Baicalein and forsythoside A are key anti-inflammatory active substances. Chlorogenic acid and forsythoside A exhibit antiviral activity. This study clarifies the main chemical material basis of Shuanghuanglian preparations and their underlying antibacterial, anti-inflammatory, and antiviral mechanisms, thus providing theoretical support for further research and clinical application. However, the molecular mechanisms of some compounds remain unclear. Future studies should focus on further mechanistic and clinical research to promote the optimization and application of Shuanghuanglian preparations.

Keywords

shuanghuanglian preparations chemical components pharmacological effects

1. Introduction

Shuanghuanglian preparations consist of three medicinal herbs: Flos Lonicerae(Lonicera japonica Thunb.), Radix Scutellariae (Scutellaria baicalensis Georgi), and Fructus Forsythiae(Forsythia suspensa(Thunb.)Vahl).¹ This formula is widely used in traditional Chinese medicine for its effects in relieving wind-heat exterior syndrome and clearing heat and toxins. It is clinically indicated for fever, cough, and sore throat caused by exogenous wind-heat, as well as for early-stage warm pathogen diseases and various heat-toxin conditions.^2,3 The combination of Flos Lonicerae and Fructus Forsythiae disperses exterior pathogens,⁴ while Radix Scutellariae clears internal heat,⁵ exerting synergistic effects which embodies the classic “monarch-minister-assistant-guide” compatibility principle of Chinese herbal formulas.

Modern pharmacological studies have demonstrated that Shuanghuanglian preparations possess significant antibacterial, anti-inflammatory, antiviral, and immunomodulatory activities.^6-9 Various dosage forms, including injections, oral liquids, granules, and capsules, have been developed and widely used in clinical settings.¹⁰ However, most existing studies have focused on the chemical constituents and bioactivities of individual herbs, lacking a systematic understanding of the synergistic mechanisms among the three components. In particular, the pharmacodynamic material basis and molecular mechanisms of many compounds, such as iridoid glycosides and volatile oils in Flos Lonicerae,^11,12 phenylpropanoids, terpenoids, and steroids in Radix Scutellariae,^13,14 and lignans and phenylethanoid glycosides in Fructus Forsythiae¹⁵—remain poorly understood, which hinders its further development and precise clinical application.

Network pharmacology has emerged as a powerful tool for constructing “drug–target–disease” networks, offering a new paradigm for elucidating the multi-component, multi-target, and multi-pathway mechanisms of Chinese herbal formulas.^16,17 Nevertheless, a comprehensive integration of the chemical components, pharmacological effects, and network pharmacology analysis of the three herbs in Shuanghuanglian preparations is still lacking. Existing studies are largely fragmented, limiting a holistic understanding of the “component–target–efficacy” relationship.

To address this gap, this study systematically reviews the chemical constituents of the three herbs and their antibacterial, anti-inflammatory, and antiviral pharmacological effects. Network pharmacology was used to construct a “herb–active ingredient–target” network. The aim is to elucidate the pharmacodynamic material basis and potential mechanisms of Shuanghuanglian preparations, thereby providing theoretical support for quality control, formulation optimization, and rational clinical use, as well as offering insights for the modernization of Chinese herbal medicine research.

2. The Primary Chemical Constituents of Flos Lonicerae

Flos Lonicerae, derived from the dried flower buds or initial blooms of Lonicera japonica Thunb, is characterized by a sweet flavor and cold property. It is clinically indicated for conditions including carbuncles, furuncle, pharyngitis, acute bacillary dysentery with bloody-purulent stool, common cold due to wind-heat, and febrile diseases.¹ Recent studies by domestic and international researchers have identified its primary chemical constituents as: flavonoids, organic acids, iridoid glycosides, volatile oils, and saponins. These compounds demonstrate broad-spectrum pharmacological activities including anti-inflammatory, antibacterial, antiviral, and antioxidant effects.¹⁸ Representative flavonoid compounds are cataloged in Table 1, with corresponding structural diagrams provided in Table 2. Non-flavonoid representative compounds are detailed in Table 3.

Table 1.

The Representative Flavonoid Compounds in Flos Lonicerae

Item number	Systematic name	Molecular formula	Molecular weight	References
1	3,5-Dihydroxy-3′-Methoxyflavone-7-O-β-D-Glucopyranoside	C₂₂H₂₂O₁₁	462.407	19
2	Quercetin-3-O-Glucopyranoside	C₂₁H₂₀O₁₂	464.383	19
3	3,5,3′-Trihydroxyflavone-7-O-β-D-Glucopyranoside	C₂₁H₂₀O₁₁	448.380	19
4	Gossypin	C₂₁H₂₀O₁₃	480.378	19
5	Nicotiflorin	C₂₇H₃₀O₁₅	594.522	19
6	Narcissin	C₂₈H₃₂O₁₆	624.552	19
7	Rutin	C₂₇H₃₀O₁₆	610.521	19
8	Quercetin-5-Glucoside	C₂₁H₂₀O₁₂	464.383	19
9	Luteolin-7-O-Neohesperidoside	C₂₇H₃₀O₁₅	594.522	19
10	Astragalin	C₂₁H₂₀O₁₁	448.380	19
11	Isorhamnetin	C₁₆H₁₂O₇	316.265	20
12	5′-Methoxyhydnocarpin-D	C₂₆H₂₂O₁₀	494.452	21
13	Hyperoside	C₂₁H₂₀O₁₂	464.379	22
14	Cynaroside	C₂₁H₂₀O₁₁	448.383	22
15	Quercetin	C₁₅H₁₀O₇	302.238	22
16	Apigenin	C₁₅H₁₀O₅	270.240	22
17	Luteolin	C₁₅H₁₀O₆	286.239	23
18	Rhoifolin	C₂₇H₃₀O₁₄	578.527	23

Table 2.

Structural Diagram of the Representative Flavonoid Compounds in Flos Lonicerae

Flavonoid skeleton
Item number	R₁	R₂	R₃	R₄	R₅	R₆
1	OH	OH		OCH₃	H	H
2		OH	OH	OH	OH	H
3	OH	OH		OH	H	H
4	OH	OH		OH	OH	H
5		OH	OH	H	OH	H
6		OH	OH	OCH₃	OH	H
7		OH	OH	OH	OH	H
8	OH		OH	OH	OH	H
9	H	OH		OH	OH	H
10		OH	OH	H	OH	H
11	OH	OH	OH	OH	OH	H
12	OH	H			OH	OCH₃
13		OH	OH	H	OH	OH
14	H	OH		H	OH	OH
15	OH	OH	OH	H	OH	OH
16	H	OH	OH	H	OH	H
17	H	OH	OH	H	OH	OH
18	H	OH		H	OH	H

Table 3.

Representative Non-flavonoid Compounds in Flos Lonicerae

Taxonomy	Systematic name	Molecular formula	Molecular weight	References
Organic Acids	Vanillic Acid	C₈H₈O₄	168.148	20
	p-Hydroxybenzoic Acid	C₇H₆O₃	138.122	20
	Benzoic Acid	C₇H₆O₂	122.123	21
	Tetrapedic Acid B	C₂₂H₄₄O₄	372.590	21
	Chlorogenic Acid	C₁₆H₁₈O₉	354.311	22
	Isochlorogenic Acid A	C₂₅H₂₄O₁₂	516.455	22
	Isochlorogenic Acid B	C₂₅H₂₄O₁₂	516.455	22
	Isochlorogenic Acid C	C₂₅H₂₄O₁₂	516.455	22
	Caffeic Acid	C₉H₈O₄	180.159	22
	Neochlorogenic Acid	C₁₆H₁₈O₉	354.314	22
	Propionic Acid	C₃H₆O₂	74.079	22
	4-(4,6-Diamino-s-triazinyl)-2,5-Dichlorophenol	C₉H₇Cl₂N₅O	272.089	22
	1,2,4-Benzenetriol	C₆H₆O₃	126.111	22
	Cryptochlorogenic Acid Methyl Ester	C₁₇H₂₀O₉	368.338	22
	1-Caffeoylquinic Acid	C₁₆H₁₈O₉	354.311	22
	Cryptochlorogenic Acid	C₁₆H₁₈O₉	354.314	22
	3,4-Dihydroxybenzoic Acid	C₇H₆O₄	154.121	22
	Cis-p-Coumaric Acid	C₉H₈O₃	164.160	22
	Ethyl Caffeate	C₁₁H₁₂O₄	208.213	22
	Ethyl Dodecanoate	C₁₄H₂₈O₂	228.376	22
	Caffeic Acid Methyl Ester	C₁₀H₁₀O₄	194.186	22
	Cinnamic Acid	C₉H₈O₂	148.161	23
	Quinic Acid	C₇H₁₂O₆	192.167	23
	Ferulic Acid	C₁₀H₁₀O₄	194.186	23
	Kaempferol	C₁₅H₁₀O₆	286.239	24
	Lonfuranacid A	C₁₂H₂₀O₅	244.287	25
	Lonfuranacid B	C₁₂H₂₀O₅	244.287	25
Iridoid Glycosides	Loganic Acid	C₁₆H₂₄O₁₀	376.361	22
	Loganin	C₁₇H₂₆O₁₀	390.385	22
	Morroniside	C₁₇H₂₆O₁₁	406.384	22
	Secoxyloganin	C₁₇H₂₄O₁₁	404.371	22
	8-epi-loganic Acid	C₁₆H₂₄O₁₀	376.361	22
	8-Epiloganin	C₁₇H₂₆O₁₀	390.387	22
	Vogeloside	C₁₇H₂₄O₁₀	388.372	22
	7-O-Ethylmorroniside	C₁₉H₃₀O₁₁	434.438	22
	Secologanic Acid	C₁₆H₂₂O₁₀	374.342	22
	7-Ketologanin	C₁₇H₂₄O₁₀	388.372	22
	Kingiside	C₁₇H₂₄O₁₁	404.371	22
	Centauroside	C₃₄H₄₆O₁₉	758.723	23
	Swertiamarin	C₁₆H₂₂O₁₀	374.342	23
	Tetraacetylsecologanin	C₂₅H₃₂O₁₄	556.521	23
	Sweroside	C₁₆H₂₂O₉	358.343	26
Volatile Oils	6,7,10-Trihydroxy-8-Octadecenoic Acid	C₁₈H₃₄O₅	330.465	21
	2-Heptadecanone	C₁₇H₃₄O	254.456	22
	Dibutyl Phthalate	C₁₆H₂₂O₄	278.348	22
	2-Nonadecanone	C₁₉H₃₈O	282.512	22
	2,4-Di-tert-Butylphenol	C₁₄H₂₂O	206.329	22
	6,10,14-Trimethylpentadecan-2-One	C₁₈H₃₆O	268.485	22
	Doconexent	C₂₂H₃₂O₂	328.496	22
	Methyl Linoleate	C₁₉H₃₄O₂	294.479	22
	Nonacosane	C₂₉H₆₀	408.799	22
	Hentriacontane	C₃₁H₆₄	436.853	22
	Palmitic Acid	C₁₆H₃₂O₂	256.430	22
	Methyl Palmitate	C₁₇H₃₄O₂	270.457	22
	Methyl Elaidolinolenate	C₁₉H₃₂O₂	292.463	22
	Methyl Linolenate	C₁₉H₃₂O₂	292.463	22
Saponins	Macranthoidin A	C₅₉H₉₆O₂₇	1237.390	27
	Macranthoidin B	C₆₅H₁₀₆O₃₂	1399.531	27
	Kalopanaxsaponin H	C₄₇H₇₆O₁₇	913.108	27
	Macranthoside B	C₅₃H₈₆O₂₂	1075.249	27
	Dipsacoside B	C₅₃H₈₆O₂₂	1075.249	27
	Asperosaponin VI	C₄₇H₇₆O₁₈	929.107	27
	Hederagenin	C₃₀H₄₈O₄	472.710	27
Others	stigmasterol	C₂₉H₄₈O	412.702	20
	Sitogluside	C₃₅H₆₀O₆	576.859	21
	n-(3-Iodobenzyl)-5′-O-Methyladenosine	C₁₈H₂₀IN₅O₄	497.292	22
	2′-O-Methyladenosine	C₁₁H₁₅N₅O₄	281.272	22
	Adenosine	C₁₀H₁₃N₅O₄	267.245	22
	6-(Hydroxymethyl)pyridin-3-ol	C₆H₇NO₂	125.127	22
	Leucine	C₆H₁₃NO₂	131.175	23
	Uridine	C₉H₁₂N₂O₆	244.203	23
	Sucrose	C₁₂H₂₂O₁₁	342.297	23
	Arginine	C₆H₁₄N₄O₂	174.204	27
	Valine	C₅H₁₁NO₂	117.148	27
	Tyrosine	C₉H₁₁NO₃	181.191	27
	l-Isoleucine	C₆H₁₃NO₂	131.175	27
	Phenylalanine	C₉H₁₁NO₂	165.192	27
	Eleutheroside B	C₁₇H₂₄O₉	372.372	28

3. The Primary Chemical Constituents of Radix Scutellariae

Radix Scutellariae, derived from the dried roots of Scutellaria baicalensis Georgi, exhibits a bitter flavor and cold property. It possesses therapeutic actions including heat-clearing, fetus-calming, fire-purging, toxin-resolving, and hemostasis.¹ Pharmacological studies confirm its significant antibacterial, anti-inflammatory, antiviral, and antioxidant activities.²⁹ Research indicates abundant chemical constituents primarily comprising flavonoids, phenylpropanoids, volatile oils, terpenoids, and steroids. Representative compounds are cataloged in Table 4.

Table 4.

The Main Representative Compounds in Radix Scutellariae

Taxonomy	Systematic name	Molecular formula	Molecular weight	References
Flavonoids	5,7,2′,6′-Tetrahydroxyflavone	C₁₅H₁₀O₆	286.241	29
	Cirsimaritin	C₁₇H₁₄O₆	314.293	29
	Isoliquiritigenin	C₁₅H₁₂O₄	256.257	29
	Scutellarein	C₁₅H₁₀O₆	286.239	29
	Norwogonin	C₁₅H₁₀O₅	270.240	29
	Luteolin	C₁₅H₁₀O₆	286.239	29
	Genkwanin	C₁₆H₁₂O₅	284.267	29
	Apigenin-7-O-Beta-D-Glucuronide	C₂₁H₁₈O₁₁	446.364	29
	Scutellarin	C₂₁H₁₈O₁₂	462.363	29
	5,4′-Dihydroxy-6,7,8,3′-Tetramethoxyflavone	C₁₉H₁₈O₈	374.345	29
	5,2′-dihydroxy-7,8-Dimethoxyflavone	C₁₇H₁₄O₆	314.293	29
	Apigenin-7-O-β-D-glucoside	C₂₁H₂₀O₁₀	432.381	29
	5,2′-Dihydroxy-6,7,8-Trimethoxyflavone	C₁₈H₁₆O₇	344.321	29
	5,7,2′-Trihydroxy-6-Methoxyflavone	C₁₆H₁₂O₆	300.268	29
	5,7,2′-Trihydroxy-6,8-Dimethoxyflavone	C₁₇H₁₄O₇	330.294	29
	5,6,7-Trihydroxy-4′-Methoxyflavone	C₁₆H₁₂O₆	300.268	29
	Hispidulin	C₁₆H₁₂O₆	300.266	30
	4′,5-Dihydroxy-3′,5′,6,7-Tetramethoxyflavone	C₁₉H₁₈O₈	374.347	30
	Isoscutellarein	C₁₅H₁₀O₆	286.241	30
	Apigenin	C₁₅H₁₀O₅	270.240	30
	Wogonin	C₁₆H₁₂O₅	284.267	31
	Baicalein	C₁₅H₁₀O₅	270.240	31
	Viscidulin III	C₁₇H₁₄O₈	346.293	31
	Viscidulin I	C₁₅H₁₀O₇	302.238	32
	Oroxindin	C₂₂H₂₀O₁₁	460.391	32
	Chrysin	C₁₅H₁₀O₄	254.241	32
	Oroxylin A	C₁₆H₁₂O₅	284.267	32
	3′,4′,5′,5,7-Pentamethoxyflavone	C₂₀H₂₀O₇	372.375	33
Dihydroflavones and their glycosides	Carthamidin	C₁₅H₁₂O₆	288.255	29
	Isocarthamidin	C₁₅H₁₂O₆	288.257	29
	5,6,7-Trihydroxy-4′-Methoxyflavanone	C₁₆H₁₄O₆	302.282	29
	(2S)-5,7,2′-Trihydroxy-6-Methoxydihydroflavone	C₁₆H₁₄O₆	302.282	29
	(2S)-5,7-Dihydroxy-6,4′-Dimethoxyflavanone	C₁₇H₁₆O₆	316.309	29
	5,4′-Dihydroxy-7-Methoxyflavanone	C₁₆H₁₄O₅	286.284	29
	Dihydrooroxylin A	C₁₆H₁₄O₅	286.284	31
	5-Methoxy-7-Hydroxydihydroflavone	C₁₆H₁₄O₄	270.284	31
	(2S)-5,7,2′-Trihydroxydihydroflavone-6′-O-β-D-Glucopyranoside	C₂₁H₂₂O₁₂	466.395	32
	(2R,3R)-3,5,7,2′,6′-Pentahydroxyflavanone	C₁₅H₁₂O₇	304.256	32
	(2S)-5,7,2′,6′-Tetrahydroxydihydroflavone	C₁₅H₁₂O₆	288.255	32
Phenylpropanoids	Syringin	C₁₇H₂₄O₉	372.372	29
	5-Hydroxycoumarin	C₉H₆O₃	162.144	29
	8-Hydroxycoumarin	C₉H₆O₃	162.144	29
	8-(4′-Hydroxybenzene)-coumarin	C₁₅H₁₀O₃	238.250	29
	Caffeic Acid Methyl Ester	C₁₀H₁₀O₄	194.186	29
	Caffeic Acid	C₉H₈O₄	180.159	29
	Methyl Ferulate	C₁₁H₁₂O₄	208.213	29
	Verbascoside	C₂₉H₃₆O₁₅	624.592	32
	Cistanoside D	C₃₁H₄₀O₁₅	652.650	32
	4-O-β-D-Glucopyranosyl-trans-cinnamic Acid	C₁₄H₁₉O₈	315.108	34
	4-O-β-D-Glucopyranosyl-cis-cinnamic Acid	C₁₄H₁₉O₈	315.108	34
	4-Hydroxy-3,5-Dimethoxybenzaldehyde	C₉H₁₀O₄	182.175	35
	Vanillin	C₈H₈O₃	152.149	35
	Salidroside	C₁₄H₂₀O₇	300.307	36
	Darendoside A	C₁₉H₂₈O₁₁	432.422	36
	Darendoside B	C₂₁H₃₂O₁₂	476.478	36
	Martynoside	C₃₁H₄₀O₁₅	652.646	36
Volatile Oils	Cyclohexanone	C₆H₁₀O	98.145	37
	Benzaldehyde	C₇H₆O	106.124	37
	Phenylacetaldehyde	C₈H₈O	120.151	37
	Beta-Pinene	C₁₀H₁₆	136.237	37
	Benzyl Alcohol	C₇H₈O	108.140	37
	Beta-Ocimene	C₁₀H₁₆	136.238	37
	Gamma-Terpinene	C₁₀H₁₆	136.238	37
	Decanal	C₁₀H₂₀O	156.269	37
	Phenylethyl Alcohol	C₈H₁₀O	122.167	37
	Nonanal	C₉H₁₈O	142.242	37
	2′-Hydroxyacetophenone	C₈H₈O₂	136.150	37
	Megastigmatrienone	C₁₃H₁₈O	190.285	37
	4-Phenyl-3-Buten-2-ol	C₁₀H₁₂O	148.205	37
	2,6,11-Trimethyldodecane	C₁₅H₃₂	212.421	37
	Indole	C₈H₇N	117.151	37
	Isosativene	C₁₅H₂₄	204.357	37
	Eicosane	C₂₀H₄₂	282.556	37
	Beta-Ionone	C₁₃H₂₀O	192.302	37
	Farnesyl Acetate	C₁₇H₂₈O₂	264.408	37
	Beta-Sesquiphellandrene	C₁₅H₂₄	204.357	37
	Alpha-Muurolene	C₁₅H₂₄	204.357	37
	Muscalure	C₂₃H₄₆	322.621	37
	Caryophyllene	C₁₅H₂₄	204.357	37
	γ-Elemene	C₁₅H₂₄	204.356	37
	Acetophenone	C₈H₈O	120.151	37
	Cis-1,3-Dimethylcyclohexane	C₈H₁₆	112.216	38
	Isobutyric Acid	C₄H₈O₂	88.106	38
	Butyric Acid	C₄H₈O₂	88.106	38
	Nonane	C₉H₂₀	128.259	38
	1-Octen-3-Ol	C₈H₁₆O	128.215	38
	Dodecane	C₁₂H₂₆	170.340	38
	Tetradecane	C₁₄H₃₀	198.394	38
	2-Methoxy-4-Vinylphenol	C₉H₁₀O₂	150.177	38
	Tricosane	C₂₃H₄₈	324.637	38
	Cyclohexane	C₆H₁₂	84.162	39
	Alpha-Humulene	C₁₅H₂₄	204.357	39
	Beta-Patchoulene	C₁₅H₂₄	204.357	40
	Alpha-Guaiene	C₁₅H₂₄	204.357	40
	Menthone	C₁₀H₁₈O	154.253	40
	Palmitic Acid	C₁₆H₃₂O₂	256.430	40
	Stearic Acid	C₁₈H₃₆O₂	284.484	40
Terpenoids	Eucalyptol	C₁₀H₁₈O	154.253	36
	Camphor	C₁₀H₁₆O	152.237	36
	Isoborneol	C₁₀H₁₈O	154.253	36
	Germacrene D	C₁₅H₂₄	204.357	36
	Beta-Selinene	C₁₅H₂₄	204.357	36
	Shyobunone	C₁₅H₂₄O	220.355	41
Steroids	Alpha-Spinasterin	C₂₉H₄₈O	412.702	29
	Beta-Sitosterol	C₂₉H₅₀O	414.718	31
	Stigmasterol	C₂₉H₄₈O	412.702	36
	Sitogluside	C₃₅H₆₀O₆	576.859	36
Amino Acids	Glycine	C₂H₅NO₂	75.067	42
	D-Alanine	C₃H₇NO₂	89.094	42
	Gamma-Aminobutyric Acid	C₄H₉NO₂	103.121	42
	Serine	C₃H₇NO₃	105.093	42
	Proline	C₅H₉NO₂	115.132	42
	Valine	C₅H₁₁NO₂	117.148	42
	Threonine	C₄H₉NO₃	119.120	42
	L-Pyroglutamic Acid	C₅H₇NO₃	129.115	42
	L-Leucine	C₆H₁₃NO₂	137.175	42
	l-Isoleucine	C₆H₁₃NO₂	131.175	42
	Aspartic Acid	C₄H₇NO₄	133.103	42
	Glutamic Acid	C₅H₉NO₄	147.130	42
	L-Glutamine	C₅H₁₀N₂O₃	146.146	42
	Asparagine	C₄H₈N₂O₃	132.119	42
	Phenylalanine	C₉H₁₁NO₂	165.192	42
	Arginine	C₆H₁₄N₄O₂	174.204	42
	Tryptophan	C₁₁H₁₂N₂O₂	204.229	42
Trace Elements	Iron	Fe	55.845	29
	Zinc	Zn	65.390	29
	Copper	Cu	63.546	29
	Manganese	Mn	54.938	29
	Plumbum	Pb	207.200	29
	Cadmium	Cd	112.412	29
	Magnesium	Mg	24.305	39
	Calcium	Ca	40.080	39
	Potassium	K	39.098	39
	Phosphorus	P	30.974	39
	Sulfur	S	32.070	39
	Nickel	Ni	58.693	39
	Chromium	Cr	51.996	39
	Molybdenum	Mo	95.940	39
	Vanadium	V	50.944	39
	Tin	Sn	118.711	39
	Selenium	Se	78.971	39
	Silicon	Si	28.085	39
	Barium	Ba	137.330	39
	Aluminum	Al	26.982	39
	Arsenic	As	74.922	39
Polysaccharide	Xylose	C₅H₁₀O₅	150.130	42
	Mannitol	C₆H₁₄O₆	182.172	42
	D-Fructose	C₆H₁₂O₆	180.156	42
	D-Galactose	C₆H₁₂O₆	180.156	42
	D-Glucose	C₆H₁₂O₆	180.156	42
	Sucrose	C₁₂H₂₂O₁₁	342.297	42
	Maltose	C₁₂H₂₂O₁₁	342.297	42
	Trehalose	C₁₂H₂₂O₁₁	342.297	42
	Raffinose	C₁₈H₃₂O₁₆	504.438	42
Others	Methyl pheophorbide a	C₃₆H₃₈N₄O₅	606.700	29
	Stearyl Alcohol	C₁₈H₃₈O	270.501	29
	Lutein	C₄₀H₅₆O₂	568.886	29
	Phenylacetic Acid	C₈H₈O₂	136.150	34
	Pellitorine	C₁₄H₂₅NO	223.360	35
	Dihydropiperlonguminine	C₁₆H₂₁NO₃	275.348	35
	Futoamide	C₁₈H₂₃NO₃	301.386	35
	Piperlonguminine	C₁₆H₁₉NO₃	273.332	35
	Crotepoxide	C₁₈H₁₈O₈	362.336	35
	1,1,6-Trimethyl-1,2-Dihydronaphthalene	C₁₃H₁₆	172.271	36
	Cellotetraose	C₂₄H₄₂O₂₁	666.579	39
	Phenylpropionic acid	C₉H₁₀O₂	150.177	39
	Protocatechuic Acid	C₇H₆O₄	154.121	43

4. The Primary Chemical Constituents of Fructus Forsythiae

Fructus Forsythiae, derived from the dried fruits of Forsythia suspensa Vahl, exhibits a bitter flavor and slightly cold property. It possesses therapeutic effects including heat-clearing toxin-resolving, swelling-reducing and nodule-dispersing, and wind-heat dispersing. It is clinically employed for treating carbuncles, acute mastitis, scrofula, wind-heat common cold, erysipelas, early-stage febrile diseases, warm pathogen entering the nutrient aspect, high fever with irritability, heat strangury with urinary retention, and maculae with clouded spirit.¹ The chemical composition of Fructus Forsythiae is relatively complex, primarily comprising phenolic acids, lignans, phenylethanoid glycosides, flavonoids, volatile oils, and terpenoids. Modern pharmacological studies confirming significant anti-inflammatory, antibacterial, antiviral, and antioxidant activities.⁴⁴ Representative phenolic acid compounds are cataloged in Table 5, their structural diagrams detailed in Table 6, and non-phenolic acid representative compounds presented in Table 7.

Table 5.

Representative Phenolic Acid Compounds in Fructus Forsythiae

Item number	Systematic name	Molecular formula	Molecular weight	References
1	Chlorogenic Acid	C₁₆H₁₈O₉	354.311	45
2	Syringic Acid	C₉H₁₀O₅	198.174	44
3	Gallic Acid	C₇H₆O₅	170.120	44
4	Protocatechualdehyde	C₇H₆O₃	138.122	44
5	Vanillic Acid	C₈H₈O₄	168.148	44
6	Hydroxybenzoic Acid	C₇H₆O₃	138.122	44
7	Protocatechuic Acid	C₇H₆O₄	154.121	44
8	4-Hydroxybenzyl Alcohol	C₇H₈O₂	124.139	44
9	4-Hydroxybenzaldehyde	C₇H₆O₂	122.123	44
10	1-(4-Hydroxyphenyl)-2,3-dihydroxypropan-1-one	C₉H₁₀O₄	182.175	44
11	Caffeic Acid Methyl Ester	C₁₀H₁₀O₄	194.186	44
12	3,4-Dihydroxyphenylethanol	C₈H₁₀O₃	154.165	44
13	Caffeic Acid	C₉H₈O₄	180.159	46
14	p-Coumaric Acid	C₉H₈O₃	164.160	46
15	Ferulic Acid	C₁₀H₁₀O₄	194.186	46
16	Tyrosol	C₈H₁₀O₂	138.166	47
17	4-Methoxyphenylacetaldehyde	C₉H₁₀O₂	150.177	47
18	4-Hydroxyphenylacetic Acid	C₈H₈O₃	152.149	47
19	Methyl 4-Hydroxyphenylacetate	C₉H₁₀O₃	166.176	48
20	1,2,4-Benzenetriol	C₆H₆O₃	126.111	48
21	4-Hydroxyphenethyl-2-(4-Hydroxyphenyl)Acetate	C₁₆H₁₆O₄	272.300	48
22	4-(2-Hydroxyethyl)Benzaldehyde	C₉H₁₀O₂	150.177	49

Table 6.

Structural Diagram of the Representative Phenolic Acid Compounds in Fructus Forsythiae

Phenolic acid skeleton
Item number	R₁	R₂	R₃	R₄	R₅	R₆
1	H		H	H	OH	OH
2	COOH	H	OCH₃	OH	OCH₃	H
3	COOH	H	OH	OH	OH	H
4	H	CHO	H	H	OH	OH
5	H	COOH	H	OH	OCH₃	H
6	OH	H	H	COOH	H	H
7	OH	OH	H	H	COOH	H
8	H	CH₂OH	H	H	OH	H
9	CHO	H	H	OH	H	H
10	H		H	H	OH	H
11		H	OH	OH	H	H
12	H	CH₂CH₂OH	H	H	OH	OH
13		H	H	OH	OH	H
14		H	H	OH	H	H
15		H	H	OH	OCH₃	H
16	CH₂CH₂OH	H	H	OH	H	H
17	CH₂CHO	H	H	OCH₃	H	H
18	H₂CCOOH	H	H	OH	H	H
19	H₂CCOOCH₃	H	H	OH	H	H
20	OH	H	OH	H	H	OH
21		H	H	OH	H	H
22	CHO	H	H	CH₂CH₂OH	H	H

Table 7.

Representative Non-phenolic Acid Compounds in Fructus Forsythiae

Taxonomy	Systematic name	Molecular formula	Molecular weight	References
Lignans	Pinoresinol	C₂₀H₂₂O₆	358.391	45
	Olivile	C₂₀H₂₄O₇	376.400	45
	Isolariciresinol	C₂₀H₂₄O₆	360.407	45
	Cycloolivil	C₂₀H₂₄O₇	376.405	45
	Secoisolariciresinol	C₂₀H₂₆O₆	362.422	45
	(+)-Piresil-4-O-Beta-D-Glucopyranside	C₂₆H₃₂O₁₁	520.533	45
	Dimethylmatairesinol	C₂₂H₂₆O₆	386.444	50
	Phenylbutyric Acid	C₁₀H₁₂O₂	164.204	50
	Sylvatesmin	C₂₁H₂₄O₆	372.418	51
	Phillyrin	C₂₇H₃₄O₁₁	534.560	51
	Epipinoresinol	C₂₀H₂₂O₆	358.391	51
	8-Hydroxypinoresinol	C₂₀H₂₂O₇	374.389	52
	Lariciresinol	C₂₀H₂₄O₆	360.406	53
	Cedrusin	C₁₉H₂₂O₆	346.380	53
	(+)-Piresil-4′-O-Beta-D-Glucopyraside	C₂₆H₃₂O₁₁	520.531	54
	Arctigenin	C₂₁H₂₄O₆	372.417	55
	Arctiin	C₂₇H₃₄O₁₁	534.558	55
	Matairesinoside	C₂₆H₃₂O₁₁	520.533	55
	Matairesinol	C₂₀H₂₂O₆	358.390	56
	Pinoresinol Monomethyl Ether	C₂₁H₂₄O₆	372.418	56
	Salicifoliol	C₁₃H₁₄O₅	250.250	57
	(+)-Pinoresinol-4′-O-β-D-glucopyranoside	C₂₆H₃₂O₁₁	520.533	58
	Macelignan	C₂₀H₂₄O₄	328.408	58
Phenylethanoid Glycosides	Forsythoside B	C₃₄H₄₄O₁₉	756.712	45
	Forsythoside E	C₂₀H₃₀O₁₂	462.451	45
	Forsythoside G	C₃₅H₄₆O₁₉	770.739	45
	suspensaside	C₂₉H₃₆O₁₆	640.595	45
	Salidroside	C₁₄H₂₀O₇	300.307	45
	Forsythoside F	C₃₄H₄₄O₁₉	756.712	52
	Forsythoside H	C₂₉H₃₆O₁₅	624.600	52
	Forsythoside I	C₂₉H₃₆O₁₅	624.600	52
	Forsythoside A	C₂₉H₃₆O₁₅	624.596	56
	Calceolarioside A	C₂₃H₂₆O₁₁	478.453	59
	Calceolarioside B	C₂₃H₂₆O₁₁	478.453	59
	Acteoside	C₂₉H₃₆O₁₅	624.592	60
Flavonoids	Quercetin	C₁₅H₁₀O₇	302.238	45
	Isoquercetin	C₂₁H₂₀O₁₂	464.383	45
	Rutin	C₂₇H₃₀O₁₆	610.521	45
	Kaempferol	C₁₅H₁₀O₆	286.239	45
	Isorhamnetin	C₁₆H₁₂O₇	316.265	45
	Luteolin	C₁₅H₁₀O₆	286.239	45
	Luteoloside	C₂₁H₂₀O₁₁	448.383	45
	Hesperidin	C₂₈H₃₄O₁₅	610.565	45
	Hyperoside	C₂₁H₂₀O₁₂	464.379	45
	Tiliroside	C₃₀H₂₆O₁₃	594.529	61
	Baicalin	C₂₁H₁₈O₁₁	446.364	61
	Cleroindicin C	C₈H₁₂O₃	156.181	61
	Astragalin	C₂₁H₂₀O₁₁	448.380	56
	Quercitrin	C₂₁H₂₀O₁₁	448.380	56
	Wogonin-7-O-glucoside	C₂₂H₂₂O₁₀	446.408	60
Volatile Oils and Terpenoids	Perillaldehyde	C₁₀H₁₄O	150.221	45
	3-Carene	C₁₀H₁₆	136.238	45
	Thujone	C₁₀H₁₆O	152.236	45
	(-)-Terpinen-4-ol	C₁₀H₁₈O	154.253	45
	Alpha-Phellandrene	C₁₀H₁₆	136.238	45
	Beta-Phellandrene	C₁₀H₁₆	136.238	45
	Alpha-Terpinene	C₁₀H₁₆	136.238	45
	Gamma-Terpinene	C₁₀H₁₆	136.238	45
	Camphene	C₁₀H₁₆	136.238	45
	Sabinene	C₁₀H₁₆	136.238	45
	Alpha-Thujene	C₁₀H₁₆	136.238	45
	Betulinic Acid	C₃₀H₄₈O₃	456.711	50
	p-Cymen-8-ol	C₁₀H₁₄O	150.221	50
	Geraniol	C₁₀H₁₈O	154.253	50
	Camphor	C₁₀H₁₆O	152.237	50
	Oleanolic Acid	C₃₀H₄₈O₃	456.711	51
	Octacosane	C₂₈H₅₈	394.772	57
	Myristic Acid	C₁₄H₂₈O₂	228.376	57
	Cis-Linoleic acid	C₁₇H₃₀O₂	266.424	57
	Squalene	C₃₀H₅₀	410.730	57
	Alpha-Pinene	C₁₀H₁₆	136.237	62
	Beta-Pinene	C₁₀H₁₆	136.237	62
	Limonene	C₁₀H₁₆	136.237	62
	Linalool	C₁₀H₁₈O	154.253	63
	Alpha-Terpineol	C₁₀H₁₈O	154.253	63
	Beta-Myrcene	C₁₀H₁₆	136.238	63
	Beta-Ocimene	C₁₀H₁₆	136.238	63
	p-Cymene	C₁₀H₁₄	134.222	63
	Copaene	C₁₅H₂₄	204.357	64
	Alpha-Cubebene	C₁₅H₂₄	204.357	64
	Geranic Acid	C₁₀H₁₆O₂	168.236	64
	Alpha-Cadinol	C₁₅H₂₆O	222.371	64
	Germacrene B	C₁₅H₂₄	204.357	64
	4,8,13-Duvatriene-1,3-Diol	C₂₀H₃₄O₂	306.490	64
	Mestanolone	C₂₀H₃₂O₂	304.474	64
	Isoaromadendrene Epoxide	C₁₅H₂₄O	220.350	64
	Dehydropinifolic Acid	C₂₀H₃₀O₄	334.456	65
	Alphitolic Acid	C₃₀H₄₈O₄	472.710	66
	Lupenyl acetate	C₃₂H₅₂O₂	468.766	67
	Beta-Amyrenyl Acetate	C₃₂H₅₂O₂	468.766	67
	Ursolic Acid	C₃₀H₄₈O₃	456.711	67
	Phytolaccinic Acid	C₃₁H₄₈O₆	516.719	67
Others	Erythritol	C₄H₁₀O₄	122.120	60
	Rengyoxide	C₈H₁₄O₃	158.197	60
	Cornoside	C₁₄H₂₀O₈	316.308	60
	Beta-Sitosterol	C₂₉H₅₀O	414.718	68
	(-)-Bicuculline	C₂₀H₁₇NO₆	367.358	68
	Sitogluside	C₃₅H₆₀O₆	576.859	68
	Rengyol	C₈H₁₆O₃	160.213	68
	Forsythide	C₁₆H₂₂O₁₁	390.344	68

5. Pharmacological Actions of Shuanghuanglian Preparations

Shuanghuanglian preparations exert therapeutic effects characterized by “dispelling wind and releasing the exterior” and “clearing heat and resolving toxins”. Clinically, they are indicated for fever, cough, and sore throat caused by external contraction of wind-heat.¹ These preparations are refined from extracts of three herbs: Flos Lonicerae, Radix Scutellariae, and Fructus Forsythiae. In the classification of Chinese Materia Medica, all three belong to the heat-clearing herbs category. Crucially, Flos Lonicerae and Fructus Forsythiae are classified as essential herbs for heat-clearing and toxin-resolving, while Radix Scutellariae holds primacy among heat-clearing and dampness-drying herbs.⁶⁹ Through synergistic interaction, these herbs achieve dual resolution of exterior and interior syndromes and simultaneous clearance of the clearing qi-blood (the body’s vital energy and blood, which together support physiological functions and defend against pathogens), demonstrating potent heat-clearing and toxin-resolving effects in wind-heat exterior syndromes, early-stage warm pathogen diseases, and various damp-heat patterns presenting with excess-heat manifestations.⁷⁰ Modern pharmacological studies confirm that all three herbs exhibit antibacterial, anti-inflammatory, and antiviral activities.^6-8 These pharmacological actions are associated with their chemical constituents. A systematic review of the chemical composition and pharmacological effects of these preparations are summarized (Figure 1). The Molecule Names of the screened compounds were retrieved using the TCMSP database (https://tcmspw.com/tcmsp.php). Based on the Molecule Name of each component, its Isomeric SMILES structure was obtained from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/). Subsequently, the SwissTargetPrediction database (https://www.swisstargetprediction.ch/) was employed to predict the corresponding gene targets. Finally, potential therapeutic targets were identified as the overlapping genes between compound-related targets and disease-related genes using Venny online software, and a “herb–active ingredient–target” network was constructed using Cytoscape (3.10.0). Figures 2-4 illustrate the networks specifically associated with antibacterial, anti-inflammatory, and antiviral activities, respectively. Partial information on the active components featured in these diagrams is presented in Table 8. IC₅₀ data of partial active components are listed in Table 9.

Figure 1.

The correlation diagram of chemical components and pharmacological effects in Shuanghuanglian preparations

Figure 2.

Herb–active ingredient–target network of Shuanghuanglian preparations associated with antibacterial activity (The green represents the herbs, the red represents the compounds in herbs and the purple represents the target)

Figure 3.

Herb–active ingredient–target network of Shuanghuanglian preparations associated with anti-inflammatory activity (The green represents the herbs, the purple represents the compounds in herbs and the blue-green represents the target)

Figure 4.

Herb–active ingredient–target network of Shuanghuanglian preparations associated with antiviral activity (The green represents the herbs, the orange represents the compounds in herbs and the purple represents the target)

Table 8.

Information on Selected Active Components

Disease	Figure	Herbs	Chemical composition	Active ingredients
Antibacterial	2	Flos Lonicerae	Chlorogenic acid	SHL1
		Radix Scutellariae	Baicalein	SHL2
		Radix Scutellariae	Wogonin	SHL3
		Radix Scutellariae	Oroxindin	SHL4
		Radix Scutellariae	Baicalin	SHL5
		Fructus Forsythiae	Phillyrin	SHL6
		Fructus Forsythiae	Forsythoside A	SHL7
		Fructus Forsythiae	Forsythoside B	SHL8
Anti-inflammatory	3	Radix Scutellariae	Baicalein	SHL1
		Radix Scutellariae	Baicalin	SHL2
		Fructus Forsythiae	Chlorogenic acid	SHL3
Antiviral	4	Radix Scutellariae	Baicalin	SHL1
		Flos Lonicerae	Chlorogenic acid	SHL2
		Flos Lonicerae	Ferulic Acid	SHL3
		Fructus Forsythiae	Forsythoside A	SHL4
		Flos Lonicerae	Kaempferol	SHL5
		Flos Lonicerae	Luteolin	SHL6
		Flos Lonicerae	Quercetin	SHL7
		Fructus Forsythiae	Stigmasterol	SHL8

Table 9.

Summary of IC₅₀ Values of Selected Active Compounds

Compound	Assay system	IC₅₀ value	References
Chlorogenic acid	Cell-free	3150±120 μM	71
Baicalein	Cell-free	0.966±0.065 μM	72
Wogonin	Human liver microsome	101.1 μM	73
Baicalin	HGC-27 Cell	104.1 μM	74
Phillyrin	Cell-free	1.5 μM	75
Forsythoside A	Cell-free	2155±8.5 μM	71
Forsythoside B	HEK293 Cell	6.7±0.7 μM	76
Quercetin	Huh-7 Cell	231.0 μM	77

5.1. Antibacterial Action

The three principal herbal components constituting Shuanghuanglian preparations are Flos Lonicerae, Radix Scutellariae, and Fructus Forsythiae. According to Zhou et al,⁷⁸ the primary antibacterial constituent in Flos Lonicerae is chlorogenic acid, which exerts its effect by directly disrupting bacterial cell structures. He et al⁷⁹ demonstrated that Flos Lonicerae extract exhibits antibacterial activity by interfering with the formation of bacterial biofilms (BBF). Research by Chen et al⁸⁰ revealed that the flavonoid aglycones in Radix Scutellariae, specifically baicalin, baicalein, wogonin, and wogonoside, serve as core antibacterial components. Notably, higher concentrations of baicalin correlate with increased endotoxin neutralization rates, while baicalin and baicalein exhibit synergistic antibacterial effects. Zhong et al⁸¹ identified phillyrin, forsythoside A, and forsythoside B as key antibacterial constituents in Forsythiae Fructus, with forsythoside B acting as an effective monomer for inhibiting bacterial efflux pumps. Wang et al⁸² further confirmed that phillyrin also disrupts BBF formation. Collectively, the antibacterial mechanisms of Shuanghuanglian preparations encompass: direct destruction of bacterial cell structures, endotoxin reduction to enhance immune defense, interference with BBF formation, inhibition of microbial enzyme activity, and suppression of bacterial efflux pump function.⁸³

5.2. Anti-inflammatory Action

According to reported studies,⁸⁴ the anti-inflammatory effects of Flos Lonicerae are attributed to bioactive constituents including macranthoidin A, dipsacoside B, and hederagenin. Wu et al⁸⁵ demonstrated that Flos Lonicerae extract exerts anti-inflammatory activity by suppressing the production of inflammatory mediators. Zhang et al⁸⁶ established that baicalein from Radix Scutellariae inhibits pro-inflammatory cytokines and mediators, thereby contributing to its anti-inflammatory efficacy. Relevant studies indicate Fructus Forsythiae exerts anti-inflammatory effects through chlorogenic acid and forsythoside A,^45,57 which modulate specific inflammatory pathways including NF-κB and MAPK cascades. The anti-inflammatory mechanisms of Shuanghuanglian preparations primarily derive from inhibition of vascular permeability, restriction of inflammatory cell proliferation, and suppression of inflammatory factor secretion, achieving coordinated regulation of inflammatory responses through synergistic actions of these tri-herb components.⁷⁰

5.3. Antiviral Action

According to relevant research,⁸⁷ chlorogenic acid and ferulic acid in Flos Lonicerae demonstrate significant antiviral activity. Chen et al⁸⁸ employed network pharmacology analysis to identify stigmasterol, luteolin, quercetin, and kaempferol as shared antiviral constituents in both Flos Lonicerae and Fructus Forsythiae. Zhang et al⁸⁹ revealed that forsythoside A from Forsythiae Fructus exerts antiviral effects by inhibiting viral replication. Wang et al⁹⁰ experimentally established that baicalin restricts viral entry into host cells and mitigates virus-induced inflammatory responses to confer antiviral efficacy. Shuanghuanglian preparations collectively inhibit viral activity through triple mechanisms: blockade of viral cellular invasion, suppression of viral genome replication, and interference with viral particle maturation and release processes, thereby achieving broad-spectrum antiviral coverage against enveloped viruses including influenza and coronaviruses.⁹¹

6. Conclusion

This study systematically reviews the chemical components and pharmacological mechanisms of Shuanghuanglian preparations, a classic traditional Chinese medicine formula composed of Flos Lonicerae, Radix Scutellariae, and Fructus Forsythiae. The chemical constituents of this formula are diverse, including flavonoids, organic acids, lignans, phenylethanoid glycosides, iridoid glycosides, and volatile oils. Among these, chlorogenic acid, baicalin, baicalein, and forsythoside A have been confirmed as key components responsible for its antibacterial, anti-inflammatory, and antiviral activities. Network pharmacology-based “herb–active ingredient–target” analyses have further validated the “multi-component, multi-target, multi-pathway” therapeutic characteristics of this formula, providing a theoretical foundation for its quality control, mechanistic studies, and rational clinical application.

Although significant progress has been made in the phytochemical and pharmacological research of Shuanghuanglian preparations, several limitations remain. First, most studies have followed a linear “isolation–identification–activity screening” paradigm, which insufficiently captures the synergistic mechanisms of multi-component and multi-target interactions in herbal formulas. Although network pharmacology has been introduced, the constructed networks are largely dependent on database predictions and lack rigorous experimental validation and dose–response analysis. Second, the synergistic mechanisms underlying the compatibility of the three herbs remain unclear. The traditional compatibility principle—where by Flos Lonicerae and Fructus Forsythiae disperse the exterior and clear heat, while Radix Scutellariae clears interior heat—has not been systematically elucidated at the chemical and pharmacological levels. Third, certain classes of compounds remain poorly characterized and their mechanisms of action are largely unknown, including iridoid glycosides and volatile oils in Flos Lonicerae, as well as phenylpropanoids and terpenoids in Radix Scutellariae. Fourth, high-quality evidence from individualized clinical applications is still lacking.

From the perspective of natural product research, Shuanghuanglian preparations represents an ideal model for exploring multi-component interactions in complex herbal formulas. Future studies should prioritize the systematic analysis and activity-guided characterization of understudied components, combined with in vivo metabolomics and gut microbiota analysis, to establish an integrated “component–metabolism–target–effect” chain and elucidate in vivo biotransformation pathways. Addressing these research gaps will not only promote the optimization and upgrading of Shuanghuanglian preparations but also provide methodological references for the modernization of other traditional Chinese medicine formulas.

Footnotes

ORCID iDs

Nannan Huang

Xiuyao Tan

Yiqian Shao

Xueyan Bi

Author Contributions

Conceptualization, N.H. and X.T.; methodology, N.H. and X.T.; software,Y.S.; validation, N.H. and X.T.; formal analysis, Y.S.; writing – original draft preparation, N.H.,X.T. and Y.S.; writing – review and editing, X.B.; project administration, X.B.; funding acquisition, N.H. and X.B. All authors have read and agreed to the published version of the manuscript.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was financially supported by the Postdoctoral Funding Project of Heilongjiang Province (No.LBH-Z23267) and Heilongjiang Provincial University Students’ Innovation and Entrepreneurship Training Program (National Key Supported Project, No.202510228056).

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Statement of Human and Animal Right

This article does not contain any studies with human or animal subjects.

References

National Pharmacopoeia Committee . Pharmacopoeia of the People's Republic China One:2025 edition[M]. Bejing: China Medical Science and Technology Press; 2025.

Tan

Huang

. Pharmacological Activity of Shuanghuanglian Preparation and Adverse Reactions of Its Injection. Northwest Journal of Pharmacy. 2026;41(1):303-311.

Wei

Ning

, et al. Advances in Material Basis and Quality Control of Shuanghuanglian Powder Injection. Chinese Traditional and Herbal Drugs. 2026;57(5):1958-1970.

Liu

Kang

Long

, et al. The Mechanism of Preventing and Treating COVID-19 with JinYinhua-Lianqiao Couplet Medicinals Based on Network Pharmacology. Western Journal of Traditional Chinese Medicine. 2023;36(6):19-25.

Luo

Chen

Wei

, et al. Huangqin Decoction Restores Immune Homeostasis and Inhibits Colonic Cell Apoptosis in Rats with Ulcerative Colitis by Suppressing the TXNIP/NLRP3 Pathway. Journal of Hunan University of Chinese Medicine. 2026;46(4):688-696.

Huang

, et al. A Five-Dimensional Network Meta-Analysis of Chinese Herbal Injections for Treating Acute Tonsillitis Combined With Western Medicine. Front Pharmacol. 2022;13:888073.

Zhou

Song

Jiang

, et al. Effect of Shuanghuanglian and Its Disassembled Formulas on Virulence Factors of Methicillin-Resistant Staphylococcus aureus. Journal of Li-shizhen Traditional Chinese Medicine. 2025;36(18):3455-3462.

. Clinical Effect of Shuanghuanglian Oral Liquid Combined with Ranitidine Hydrochloride Injection in Treatment of Oral Ulcer and its Influence on CRP and IL-6 Levels. Journal of Medical Information. 2025;38(15):80-84.

Yang

Shen

, et al. Exploring the Pharmacological Mechanisms of Shuanghuanglian Against T-cell Acute Lymphoblastic Leukaemia Through Network Pharmacology Combined with Molecular Docking and Experimental Validation. Pharmaceutical Biology. 2023;61(1):259-270.

10.

Jiang

Yao

Ding

. The Anaphylactic and Anti-Allergenic Properties of Shuanghuanglian: A Review. Comb Chem High Throughput Screen. 2026;29(3):367-386.

11.

Yang

Fang

Zhao

Zhang

. Separation of Five Iridoid Glycosides from Lonicerae Japonicae Flos Using High-Speed Counter-Current Chromatography and Their Anti-Inflammatory and Antibacterial Activities. Molecules. 2019;24(1):197.

12.

Zheng

Liu

Dong

, et al. Research Progress on the Extraction, Composition Analysis and Pharmacological Effects of Volatile Oil of Lonicera japonica. West China Journal of Pharmaceutical Sciences. 2025;40(3):331-337.

13.

Liu

. Research Progress on Chemical Composition and Pharmacological Effects of Huangqin (Scutellariae Radix) and Predictive Analysis of Quality Markers. Chinese Archives of Traditional Chinese Medicine. 2026;44(5):88-96.

14.

Ruan

Zhang

Wang

Huang

Rao

Cheng

. Predictive Analysis on Clinical Applications, Chemical Constituents, Pharmacological Effects, and Quality Markers of Scutellariae Radix. Journal of Li-shizhen Traditional Chinese Medicine. 2025;36(8):1534-1541.

15.

Zhou

Wang

. Research Progression on Anti-Inflammatory Effects of Natural Active Ingredients of Forsythia. Modern Journal of Integrated Traditional Chinese and Western Medicine. 2025;34(12):1725-1728.

16.

Zhang

Chang

, et al. Research Progress of Network Pharmacology in the TCM Field. Chinese Journal of Information on Traditional Chinese Medicine. 2024;31(11):186-190.

17.

Fei

, et al. Research Progress of Network Pharmacology in Chinese Herbal Compounds. Clinical Journal of Chinese Medicine. 2024;16(21):108-112.

18.

Zhu

Ren

Zheng

, et al. Research Progress in Functional Components and Bioactivity of Honeysuckle. Science and Technology of Food Industry. 2021;42(13):412-426.

19.

Wei

Shen

, et al. Flavonoid glycosides of Lonicera japonica flower buds. Chinese Traditional and Herbal Drugs. 2023;54(11):3424-3429.

20.

Wen

, et al. Chemical constituents from flower buds of Lonicera japonica. Chinese Traditional and Herbal Drugs. 2017;48(18):3689-3692.

21.

Wang

Zhou

Rong

. Chemical constituents of Lonicerae japonicae Flos. Journal of Chinese Medicinal Materials. 2016;39(09):2030-2032.

22.

Tan

Xia

, et al. Research progress on chemical constituents and pharmacology of honeysuckle. Journal of Anhui Agricultural Sciences. 2018;46(09):26-28.

23.

Gong

Liu

Cao

, et al. Rapid chemome profiling of chemical components of Lonicerae Japonicae Flos using DI-MS/MS∼(ALL). China Journal of Chinese Materia Medica. 2021;46(09):2220-2228.

24.

Liu

Song

, et al. Anti-complementary phenolic acids from Lonicera japonica. China Journal of Chinese Materia Medica. 2015;40(02):269-274.

25.

Liu

Cheng

, et al. Secondary metabolites from the flower buds of Lonicera japonica and their in vitro anti-diabetic activities. Fitoterapia. 2016;110:44-51.

26.

Yang

Liu

Wang

, et al. HPLC determination of three components in Flos Lonicerae. Chinese Journal of Pharmaceutical Analysis. 2006;26(02):168-171.

27.

Liu

, et al. Systematic analysis of chemical constitue of Lonicerae Japonicae Flos and Lonicerae Flos by UFLC-Triple-Q-TOF-MS/MS. Central South Pharmacy. 2016;14(04):363-369.

28.

Song

Guo

, et al. Studies on chemical constituents of aqueous extract of Lonicera japonica flower buds. China Journal of Chinese Materia Medica. 2015;40(17):3496-3504.

29.

Yao

Zhao

, et al. Study advances on chemical constituents and pharmacological effects of Huangqin (Scutellaria baicalensis). Liaoning Journal Traditional Chinese Medical. 2020;47(07):215-220.

30.

. Study on Chemical Constituents from Stems and Leaves of Scutellaria baicalensis. Chinese Journal of Experimental Traditional Medical Formulae. 2013;19(07):147-149.

31.

Chen

Zhang

, et al. Study on Chemical Constituents of Scutellaria baicalensis. Chinese Journal of Experimental Traditional Medical Formulae. 2011;17(01):78-80.

32.

Wang

, et al. Anti-H1N1 virus, cytotoxic and Nrf2 activation activities of chemical constituents from Scutellaria baicalensis. Journal of Ethnopharmacol. 2015;176:475-484.

33.

Wang

Yin

, et al. Chemical Constituents from Stems and Leaves of Scutellaria baicalensis. Chinese Journal of Experimental Traditional Medical Formulae. 2016;22(22):41-44.

34.

Liu

, et al. Chemical constituents from Scutellaria baicalensis Georgi. Chinese Journal of Medicinal Chemistry. 2009;19(01):59-62.

35.

Ding

Jiang

, et al. Studies on Non-flavonoid Constituents of Scutellaria baicalensis Georgi. Chinese Journal of Medicinal Chemistry. 2016;26(6):480-483+489.

36.

Huang

Nie

Kang

, et al. Research Progress on the Chemical Constituents,Pharmacological Effects and Quality Control of Huangqin (Scutellaria baicalensis). Journal of Liaoning University of TCM. 2024;26(04):88-96.

37.

Gong

Liu

, et al. Study on the volatile oil from aerial part of Scutellaria baicalensis Georgi by GC-MS. Journal of Anhui Agricultural Sciences. 2009;37(32):15844-15845.

38.

Chen

, et al. GC-MS Analysis and Bioactivity of Essential Oil from Scutellaria hainanensis. 2016;36(05):93-97.

39.

Sang

. Advances in Research on Chemical Constituents of Astragalus and Treatment of Alzheimer's Disease. Medical Information. 2019;32(13):52-55.

40.

Wen

Xiao

Wang

, et al. General situation of chemical constitutions and drug-processing of Scutellaria baicalensis Georgi. Natural Product Research and Development. 2004;16(06):575-580.

41.

Song

Wang

. Analysis of Essential Oils from Different Organs of Scutellaria baicalensis. Journal of Chinese Medicinal Materials. 2010;33(08):1265-1270.

42.

Kim

, et al. Comparative analysis of flavonoids and polar metabolites from hairy roots of Scutellaria baicalensis and Scutellaria lateriflora. World Journal of Microbiology Biotechnology. 2014;30(03):887-892.

43.

Qiao

Song

, et al. A targeted strategy to analyze untargeted mass spectral data:Rapid chemical profiling of Scutellaria baicalensis using ultra-high performance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry and key ion filtering. Journal of Chromatograpgy A. 2016;1441:83-95.

44.

Liu

Wen

Yan

, et al. Advances in Phenolic Acids from Forsythia suspensa. China Pharmacy. 2020;31(12):1516-1522.

45.

Jing

Zhang

, et al. Latest Research Progress on Chemical Constituents and Biological Activities of Forsythia suspensa. Journal of Chinese Medicinal Materials. 2023;46(01):242-251.

46.

Wang

Dai

, et al. Phillygenin inhibits LPS-induced activation and inflammation of LX2 cells by TLR4/MyD88/NF-κB signaling pathway. Journal of Ethnopharmacology. 2020;248:112361.

47.

Lee

Kim

, et al. Anti-inflammatory activity of the Decoction of Forsythia suspensa (Thunb.) Vahl is related to Nrf2 and A20. Journal of Ethnopharmacology. 2018;227(05):97-104.

48.

Yan

Xiang

Wen

, et al. Phenolic Acid from the Fruits of Forsythia suspensa (Thunb.) Vahl. Chinese Pharmaceutical Journal. 2017;52(02):105-108.

49.

Zhao

Yang

. Study of the Constituents of Phenolic Acids of Forsythia suspensa (Thunb.) Vahl. Journal Liaoning Medical University. 2016;37(03):12-14.

50.

Wang

Xia

Liu

, et al. Phytochemistry, pharmacology, quality control and future research of Forsythia suspensa (Thunb.) Vahl: A review. Journal of Ethnopharmacol. 2018;210:318-339.

51.

Fang

Zou

Liu

. Chemical Constituents of Forsythia suspensa. Chinese Journal of Natural Medicines. 2008;06(03):235-236.

52.

Dai

Duan

Liu

Yao

. A new lignan glycoside from Forsythia suspensa. Chin Journal of Natural Medicines. 2014;12(9):697-699.

53.

Chang

Hung

Min

, et al. Lignans from the Fruits of Forsythia suspensa (Thunb.) Vahl Protect High-Density Lipoprotein during Oxidative Stress. Bioscience Biotechnology, and Biochemistry. 2008;72(10):2750-2755.

54.

Wei

, et al. DNA fingerprint library construction and cluster analysis of Forsythia suspensa from different origins. Chinese Traditional and Herbal Drugs. 2016;47(05):816-820.

55.

Song

. Research advances of chemical composition of different parts of Forsythia suspensa. Northwest Pharmaceutical Journal. 2014;29(02):220-222.

56.

Luo

Zhang

. Study on Chemical Constituents of Extract of Forsythia suspense. Chinese Journal of Experimental Traditional Medical Formulae. 2013;19(3):143-146.

57.

Liu

Fang

, et al. Advances in Chemical Constituents and Pharmacological Effects of Forsythia suspensa. Journal of Shandong Medical College. 2021;43(04):308-309.

58.

Guo

Huang

Dong

. Study on chemical constituents of Forsythia suspensa. 2020;35(05): 648-652.

59.

Chen

Han

, et al. Chemical constituents of grown Fructus Forsythiae. Natural Product Research and Development. 2020;32(12):2066-2072.

60.

Feng

. Recent development of chemical components of studies Fructus Forsythiae. Journal of Henan University of Chinese Medicine. 2005;20(117):78-80.

61.

Chen

Jin

, et al. Advances in Chemical Constituents and Pharmacological Activities of the Medicinal Herb Forsythia suspensa. Journal of Tianjin University of Traditional Chinese Medicine. 2021;40(02):168-175.

62.

Wei

, et al. Analysis of Major Components and Antibacterial Activity of Volatile Oil from Forsythiae Fructus in Different Origins. Chinese Journal of Experimental Traditional Medical Formulae. 2016;22(4):69-74.

63.

Tian

Shi

Wang

. Volatile Oil from Forsythia suspense: Chemical Constituents and Pharmacological Effects. Natural Product Research and Development. 2018;30(10):1834-1842.

64.

Duan

. Research on Chemical Constituents of Volatile Oil from Forsythia suspensa(Thunb)Originated in Henan. Journal of Anhui Agricultural Sciences. 2008;36(19):7963-7964.

65.

Kuo

Huang

Nian

, et al. Chemical Constituents and Anti-inflammatory Principles from the Fruits of Forsythia suspensa. Journal of Natural products. 2017;80(04):1055-1064.

66.

Zhang

, et al. Triterpenoids and steroids from the leaves of Forsythia suspensa. Chemistry of Natural Compounds. 2015;51(01):178-180.

67.

Shin

Kim

Chan-Sung Park Kim

Ok-Sun Bang . Aqueous extract of Forsythia viridissima fruits: Acute oral toxicity and genotoxicity studies. Journal of Ethnopharmacol. 2020;249:112381.

68.

Kim

Lim

. Semi-Continuous Subcritical Water Extraction of Flavonoids from Citrus unshiu Peel: Their Antioxidant and Enzyme Inhibitory Activities. Antioxidants(Basel). 2020;9(05):360.

69.

Yang

Chen

, et al. Traditional Chinese Medicine Preparation Shuang-Huang-Lian in the Treatment of Influenza: A Review. J Ethnopharmacol. 2025;346:119704.

70.

Guo

Song

. Advances in Pharmacological Effects, Clinical Applications, and Adverse Reactions of Shuanghuanglian. Chin Journal of Clinical Rational Drug Use. 2017;10(07):161-163.

71.

Chen

Zhang

. Nine Different Chemical Species and Action Mechanisms of Pancreatic Lipase Ligands Screened Out from Forsythia suspensa Leaves All at One Time. Molecules. 2017;22(5):795.

72.

Zhang

Wang

, et al. Discovery of quinazolin-4-one-based non-covalent inhibitors targeting the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro). Eur J Med Chem. 2023;257:115487.

73.

Guo

, et al. Inhibitory effects of wogonin on catalytic activity of cytochrome P450 enzyme in human liver microsomes. Eur J Drug Metab Pharmacokinet. 2011;36(4):249-256.

74.

Wang

Jiang

Liu

, et al. Mechanism of baicalin inhibiting gastric cancer cells HGC-27. Journal of Regional Anatomy and Operative. 2026;35(01):7-11.

75.

Zhang

Yao

, et al. Comparative inhibitory effects of phillyrin and phillygenin on elastase: mechanisms and therapeutic potential. Front Nutr. 2026;13:1723757.

76.

Zhang

Sun

, et al. Pharmacological Inhibition of the Temperature-Sensitive and Ca²⁺-Permeable Transient Receptor Potential Vanilloid TRPV3 Channel by Natural Forsythoside B Attenuates Pruritus and Cytotoxicity of Keratinocytes. J Pharmacol Exp Ther. 2019;368(1):21-31.

77.

Xie

Bai

Qin

, et al. Investigating Mechanism of Quercetin in Inhibiting Malignant Phenotype of Hepatocellular Carcinoma Cells Based on Glycolysis Pathway [J/OL]. Chinese Journal of Experimental Traditional Medical Formulae. 2026:1-14. doi:10.13422/j.cnki.syfjx.20260266.

78.

Zhou

Luo

Xiong

, et al. Antimicrobial mechanisms of 3-O-caffeoyl quinic acid and 3,5-di-O-caffeoyl quinic acid against Escherichia coli. Food Science and Technology. 2014;39(03):228-232.

79.

Zhang

Yang

, et al. A Study on the Anti-Staphylococcus aureus Activity of Lonicera japonica Extract. Guizhou Journal of Animal Husbandry & Veterinary Medicine. 2013;37(04):11-14.

80.

Chen

Xie

Xiong

, et al. Reverse effect of baicalin/baicalein on antibiotic resistance of methicillin-resistant Staphylococcus aureus. China Pharmacy. 2008;19(09):644-646.

81.

Zhong

Zhang

Cai

. Influence of forsythoside B on efflux pump activity of Klebsiella pneumoniae. Chinese Journal of New Drugs and Clinical Remedies. 2013;32(04):303-306.

82.

Wang

Cheng

. Effect of Forsythin on the Adhesion Ability and Biofilm Formation Capacity of Pseudomonas aeruginosa. Chinese Traditional Patent Medicine. 2013;35(04):832-834.

83.

Liu

Chen

. Research Progress on Antibacterial Functions and Mechanisms of Shuanghuanglian. Journal of Yichun College. 2017;39(09):16-19.

84.

Chen

Dou

, et al. Advances in Studies on Chemical and Pharmacological Effects of Lonicerae Japonicae Flos、Lonicerae Similis Flos and Lonicerae Flos. Chinese Journal of Ethnomedicine and Ethnopharmacy. 2023;32(15):67-72.

85.

Wang

. Chemical constituents and pharmacological effect of lonicerae japonicae flos. Chinese Journal of Experimental Traditional Medical Formulae. 2019;25(04):225-234.

86.

Zhang

Liu

, et al. In vitro anti-inflammatory and antioxidative activity of baicalein. Journal of Yantai University. 2018;31(03):232-238.

87.

Luo

Wang

, et al. Advances in Anti-viral Chemical Constituents and Their Mechanism of Action from Lonicera japonica. Journal of Shaanxi University of Chinese Medicine. 2024;47(02):138-143.

88.

Chen

Gao

, et al. Elucidating the Therapeutic Mechanism of Shuanghuanglian Oral Liquid for COVID-19 through a Combination of Network Pharmacology and Molecular Docking. Journal of Shenyang Pharmaceutical University. 2022;39(05):563-574.

89.

Zhang

Liu

Yang

, et al. Effect of forsythoside A on expression of intracellular receptors and antiviral gene in IBV-infected cells. Journal Beijing University Agriculture. 2017;32(01):37-42.

90.

Wang

Zhong

. Research progress on mechanism of baicalin against influenza virus. Drugs & Clinic. 2024;39(11):2983-2987.

91.

Chen

Liu

Gao

, et al. Pharmacological activity and quality evaluation method of Shuanghuanglian oral liquid. Journal of Liaoning University of TCM. 2016;18(07):161-163.